Examination of clinical and cognitive insight in acute schizophrenia patients.

PubMed

Greenberger, Cheryl; Serper, Mark R

2010-07-01

Lack of insight or awareness of illness is a hallmark feature of schizophrenic illness and has become an increasingly important area of investigation. Although clinical insight focuses on awareness of illness factors, the concept of cognitive insight focuses on the cognitive processes involved in correcting erroneous judgments and certainty about mistaken judgments. The present study was aimed at further investigating the clinical utility and the statistical coherence of the Beck Cognitive Insight Scale (BCIS) (Beck et al., 2004) in acute schizoaffective and schizophrenia (SZ) patients. The present study examined the internal consistency of the scale, as well as its discriminative and predictive validity relative to a well-established traditional measure of clinical insight in a sample of 50 DSM-IV diagnosed SZ patients, presenting for acute inpatient treatment. The BCIS was found to be an internally consistent and a coherent measure of cognitive insight. The BCIS was unassociated with clinical insight, indicating the 2 constructs share little empirical overlap. Cognitive insight was found to be inversely associated with patients' severity of autistic preoccupation symptoms such that those individuals with more cognitive insight, exhibited fewer autistic/cognitive symptoms. Patients' clinical insight, however, was found to be inversely associated specifically with patients' severity of depression. Additionally, clinical insight was also found to be more impaired in patients residing in nursing home environments relative to their counterparts living in less restrictive settings when outside the hospital. Results are discussed in terms of the relationship between clinical and cognitive insight constructs to SZ symptom domains.

HDGF: a novel jack-of-all-trades in cancer.

PubMed

Bao, Cihang; Wang, Jianbo; Ma, Wei; Wang, Xintong; Cheng, Yufeng

2014-12-01

HDGF is an important regulator of a broad range of cancer cell activities and plays important roles in cancer cell transformation, apoptosis, angiogenesis and metastasis. Such a divergent influence of HDGF on cancer cell activities derives from its multiple inter- and sub-cellular localizations where it interacts with a range of different binding partners. Interestingly, high levels of HDGF could be detected in patients' serum of some cancers. This review is focused on the role of HDGF in tumorigenesis and metastasis, and provides insight for application in clinical cancer therapy as well as its clinical implications as a prognostic marker in cancer progression.

Mesenchymal Stem Cells from Adipose Tissue in Clinical Applications for Dermatological Indications and Skin Aging.

PubMed

Gaur, Meenakshi; Dobke, Marek; Lunyak, Victoria V

2017-01-20

Operating at multiple levels of control, mesenchymal stem cells from adipose tissue (ADSCs) communicate with organ systems to adjust immune response, provide signals for differentiation, migration, enzymatic reactions, and to equilibrate the regenerative demands of balanced tissue homeostasis. The identification of the mechanisms by which ADSCs accomplish these functions for dermatological rejuvenation and wound healing has great potential to identify novel targets for the treatment of disorders and combat aging. Herein, we review new insights into the role of adipose-derived stem cells in the maintenance of dermal and epidermal homeostasis, and recent advances in clinical applications of ADSCs related to dermatology.

Prostaglandins and Inflammation

PubMed Central

Ricciotti, Emanuela; FitzGerald, Garret A.

2011-01-01

Prostaglandins are lipid autacoids derived from arachidonic acid. They both sustain homeostatic functions and mediate pathogenic mechanisms, including the inflammatory response. They are generated from arachidonate by the action of cyclooxygenase (COX) isoenzymes and their biosynthesis is blocked by nonsteroidal anti-inflammatory drugs (NSAIDs), including those selective for inhibition of COX-2. Despite the clinical efficacy of NSAIDs, prostaglandins may function in both the promotion and resolution of inflammation. This review summarizes insights into the mechanisms of prostaglandin generation and the roles of individual mediators and their receptors in modulating the inflammatory response. Prostaglandin biology has potential clinical relevance for atherosclerosis, the response to vascular injury and aortic aneurysm. PMID:21508345

Mesenchymal Stem Cells from Adipose Tissue in Clinical Applications for Dermatological Indications and Skin Aging

PubMed Central

Gaur, Meenakshi; Dobke, Marek; Lunyak, Victoria V.

2017-01-01

Operating at multiple levels of control, mesenchymal stem cells from adipose tissue (ADSCs) communicate with organ systems to adjust immune response, provide signals for differentiation, migration, enzymatic reactions, and to equilibrate the regenerative demands of balanced tissue homeostasis. The identification of the mechanisms by which ADSCs accomplish these functions for dermatological rejuvenation and wound healing has great potential to identify novel targets for the treatment of disorders and combat aging. Herein, we review new insights into the role of adipose-derived stem cells in the maintenance of dermal and epidermal homeostasis, and recent advances in clinical applications of ADSCs related to dermatology. PMID:28117680

New insight in expression, transport, and secretion of brain-derived neurotrophic factor: Implications in brain-related diseases

PubMed Central

Adachi, Naoki; Numakawa, Tadahiro; Richards, Misty; Nakajima, Shingo; Kunugi, Hiroshi

2014-01-01

Brain-derived neurotrophic factor (BDNF) attracts increasing attention from both research and clinical fields because of its important functions in the central nervous system. An adequate amount of BDNF is critical to develop and maintain normal neuronal circuits in the brain. Given that loss of BDNF function has been reported in the brains of patients with neurodegenerative or psychiatric diseases, understanding basic properties of BDNF and associated intracellular processes is imperative. In this review, we revisit the gene structure, transcription, translation, transport and secretion mechanisms of BDNF. We also introduce implications of BDNF in several brain-related diseases including Alzheimer’s disease, Huntington’s disease, depression and schizophrenia. PMID:25426265

An analysis of a digital variant of the Trail Making Test using machine learning techniques.

PubMed

Dahmen, Jessamyn; Cook, Diane; Fellows, Robert; Schmitter-Edgecombe, Maureen

2017-01-01

The goal of this work is to develop a digital version of a standard cognitive assessment, the Trail Making Test (TMT), and assess its utility. This paper introduces a novel digital version of the TMT and introduces a machine learning based approach to assess its capabilities. Using digital Trail Making Test (dTMT) data collected from (N = 54) older adult participants as feature sets, we use machine learning techniques to analyze the utility of the dTMT and evaluate the insights provided by the digital features. Predicted TMT scores correlate well with clinical digital test scores (r = 0.98) and paper time to completion scores (r = 0.65). Predicted TICS exhibited a small correlation with clinically derived TICS scores (r = 0.12 Part A, r = 0.10 Part B). Predicted FAB scores exhibited a small correlation with clinically derived FAB scores (r = 0.13 Part A, r = 0.29 for Part B). Digitally derived features were also used to predict diagnosis (AUC of 0.65). Our findings indicate that the dTMT is capable of measuring the same aspects of cognition as the paper-based TMT. Furthermore, the dTMT's additional data may be able to help monitor other cognitive processes not captured by the paper-based TMT alone.

Insight change in psychosis: relationship with neurocognition, social cognition, clinical symptoms and phase of illness.

PubMed

Quee, P J; van der Meer, L; Krabbendam, L; de Haan, L; Cahn, W; Wiersma, D; van Beveren, N; Pijnenborg, G H M; Mulder, C L; Bruggeman, R; Aleman, A

2014-02-01

Impaired insight is an important and prevalent symptom of psychosis. It remains unclear whether cognitive disturbances hamper improvements in insight. We investigated the neurocognitive, social cognitive, and clinical correlates of changes in insight. One hundred and fifty-four patients with a psychotic disorder were assessed at baseline (T0 ) and after three years (T3 ) with the Birchwood Insight Scale, the Positive And Negative Syndrome Scale, measures of neurocognition and social cognition. Linear regression analyses were conducted to examine to what extend neurocognition, social cognition, clinical symptoms and phase of illness could uniquely predict insight change. Subsequently, changes in these factors were related to insight change. Better neurocognitive performance and fewer clinical symptoms at baseline explained insight improvements. The additional effect of clinical symptoms over and above the contribution of neurocognition was significant. Together, these factors explained 10% of the variance. Social cognition and phase of illness could not predict insight change. Changes in clinical symptoms, but not changes in neurocognitive performance were associated with insight change. Neurocognitive abilities may predict, in part, the development of insight in psychosis. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Commercial strain-derived clinical Saccharomyces cerevisiae can evolve new phenotypes without higher pathogenicity.

PubMed

Pfliegler, Walter P; Boros, Enikő; Pázmándi, Kitti; Jakab, Ágnes; Zsuga, Imre; Kovács, Renátó; Urbán, Edit; Antunovics, Zsuzsa; Bácsi, Attila; Sipiczki, Matthias; Majoros, László; Pócsi, István

2017-11-01

Saccharomyces cerevisiae is one of the most important microbes in food industry, but there is growing evidence on its potential pathogenicity as well. Its status as a member of human mycobiome is still not fully understood. In this study, we characterize clinical S. cerevisiae isolates from Hungarian hospitals along with commercial baking and probiotic strains, and determine their phenotypic parameters, virulence factors, interactions with human macrophages, and pathogenicity. Four of the clinical isolates could be traced back to commercial strains based on genetic fingerprinting. Our observations indicate that the commercial-derived clinical isolates have evolved new phenotypes and show similar, or in two cases, significantly decreased pathogenicity. Furthermore, immunological experiments revealed that the variability in human primary macrophage activation after coincubation with yeasts is largely donor and not isolate dependent. Isolates in this study offer an interesting insight into the potential microevolution of probiotic and food strains in human hosts. These commensal yeasts display various changes in their phenotypes, indicating that the colonization of the host does not necessarily impose a selective pressure toward higher virulence/pathogenicity. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Theory of Mind in Schizophrenia: Associations With Clinical and Cognitive Insight Controlling for Levels of Psychopathology.

PubMed

Popolo, Raffaele; Dimaggio, Giancarlo; Luther, Lauren; Vinci, Giancarlo; Salvatore, Giampaolo; Lysaker, Paul H

2016-03-01

Poor insight in schizophrenia is a risk factor for both poor outcomes and treatment adherence. Accordingly, interest in identifying causes of poor insight has increased. This study explored whether theory of mind (ToM) impairments are linked to poor clinical and cognitive insight independent of psychopathology. Participants with schizophrenia (n = 37) and control subjects (n = 40) completed assessments of ToM with the Hinting Task and the Brüne Picture Sequencing Task, clinical insight and psychopathology with the Positive and Negative Syndrome Scale, and cognitive insight with the Beck Cognitive Insight Scale. Results indicated that the schizophrenia group had greater impairments in ToM relative to control subjects. In the schizophrenia group, the Hinting Task performance was related to both cognitive and clinical insight, with only the relationship with cognitive insight persisting after controlling for psychopathology. Picture Sequencing Task performance was related to cognitive insight only. Future research directions and clinical implications are discussed.

Insight in pediatric obsessive-compulsive disorder: associations with clinical presentation.

PubMed

Storch, Eric A; Milsom, Vanessa A; Merlo, Lisa J; Larson, Michael; Geffken, Gary R; Jacob, Marni L; Murphy, Tanya K; Goodman, Wayne K

2008-08-15

Insight has emerged as a significant treatment outcome predictor in adult obsessive-compulsive disorder (OCD), with some suggesting that OCD with poor insight represents a distinct clinical subtype. Despite its clinical relevance, limited data exist on insight in pediatric OCD patients. The present study investigated the relation between poor insight and clinical characteristics among children and adolescents with OCD (N=78, ages 6-20 years). Forty-five percent of the sample (n=35) was considered to have low levels of insight into their symptoms, as determined by clinician rating on item 11 of the Children's Yale-Brown Obsessive-Compulsive Scale. Pearson product-moment correlations showed a significant, inverse relation between insight and OCD severity. Relative to the high insight group, parents of patients with low insight reported higher levels of OCD-related impairment and family accommodation. These findings suggest that OCD with poor insight may represent a distinct clinical feature that may require more intensive and multimodal treatment approaches.

Saccharomyces boulardii: a summary of the evidence for gastroenterology clinical practice in adults and children.

PubMed

Berni Canani, R; Cucchiara, S; Cuomo, R; Pace, F; Papale, F

2011-07-01

Probiotics are viable, nonpathogenic microorganisms (bacteria or yeast) which when administered in adequate amounts, confer a health benefit on the host. At this time, Saccharomyces boulardii is the only yeast commonly used in clinical practice. Literature on this probiotic is wide and even more data become available each year. Thus, it could be problematic for a physician summarize all the best information deriving from basic research and clinical studies. With the aim to help physicians in the use of Saccharomyces boulardii, this paper focuses on the available evidences for its efficacy and safety in different diseases in adult and pediatric patients in order to provide a practical guidance for gastroenterology clinical practice. Indications and dosage for several gastrointestinal diseases for a correct use of this probiotic are provided, and recent insights on its mechanisms of action and possible future clinical application are also discussed.

Recent Advances in Allograft Vasculopathy

PubMed Central

Merola, Jonathan; Jane-Wit, Daniel D.; Pober, Jordan S.

2017-01-01

Purpose of review Despite considerable advances in controlling acute rejection, the longevity of cardiac and renal allografts remains significantly limited by chronic rejection in the form of allograft vasculopathy (AV). This review discusses recently reported mechanistic insights of AV pathogenesis as well recent clinical evaluations of new therapeutic approaches. Recent findings Although adaptive immunity is the major driver of AV, natural killer cells mediate vasculopathic changes in a transplanted mouse heart following treatment with donor-specific antibody (DSA). However, NK cells may also dampen chronic inflammatory responses by killing donor-derived tissue-resident CD4 T cells that provide help to host B cells, the source of DSA. DSA may directly contribute to vascular inflammation by inducing intracellular signaling cascades that upregulate leukocyte adhesion molecules, facilitating recruitment of neutrophils and monocytes. DSA-mediated complement activation additionally enhances endothelial alloimmunogenicity through activation of non-canonical NF-κB signaling. New clinical studies evaluating mTOR and proteasome inhibitors to target these pathways have been reported. Summary AV is a pathology resultant from several innate and adaptive alloimmune responses. Mechanistic insights from preclinical studies have identified agents that are currently being investigated in clinical trials. PMID:27898462

Pathophysiology and animal modeling of underactive bladder.

PubMed

Tyagi, Pradeep; Smith, Phillip P; Kuchel, George A; de Groat, William C; Birder, Lori A; Chermansky, Christopher J; Adam, Rosalyn M; Tse, Vincent; Chancellor, Michael B; Yoshimura, Naoki

2014-09-01

While the symptomology of underactive bladder (UAB) may imply a primary dysfunction of the detrusor muscle, insights into pathophysiology indicate that both myogenic and neurogenic mechanisms need to be considered. Due to lack of proper animal models, the current understanding of the UAB pathophysiology is limited, and much of what is known about the clinical etiology of the condition has been derived from epidemiological data. We hereby review current state of the art in the understanding of the pathophysiology of and animal models used to study the UAB.

Impaired insight into illness and cognitive insight in schizophrenia spectrum disorders: Resting state functional connectivity

PubMed Central

Gerretsen, Philip; Menon, Mahesh; Mamo, David C.; Fervaha, Gagan; Remington, Gary; Pollock, Bruce G.; Graff-Guerrero, Ariel

2015-01-01

Background Impaired insight into illness (clinical insight) in schizophrenia has negative effects on treatment adherence and clinical outcomes. Schizophrenia is described as a disorder of disrupted brain connectivity. In line with this concept, resting state networks (RSNs) appear differentially affected in persons with schizophrenia. Therefore, impaired clinical, or the related construct of cognitive insight (which posits that impaired clinical insight is a function of metacognitive deficits), may reflect alterations in RSN functional connectivity (fc). Based on our previous research, which showed that impaired insight into illness was associated with increased left hemisphere volume relative to right, we hypothesized that impaired clinical insight would be associated with increased connectivity in the DMN with specific left hemisphere brain regions. Methods Resting state MRI scans were acquired for participants with schizophrenia or schizoaffective disorder (n = 20). Seed-to-voxel and ROI-to-ROI fc analyses were performed using the CONN-fMRI fc toolbox v13 for established RSNs. Clinical and cognitive insight were measured with the Schedule for the Assessment of Insight—Expanded Version and Beck Cognitive Insight Scale, respectively, and included as the regressors in fc analyses. Results As hypothesized, impaired clinical insight was associated with increased connectivity in the default mode network (DMN) with the left angular gyrus, and also in the self-referential network (SRN) with the left insula. Cognitive insight was associated with increased connectivity in the dorsal attention network (DAN) with the right inferior frontal cortex (IFC) and left anterior cingulate cortex (ACC). Conclusion Increased connectivity in DMN and SRN with the left angular gyrus and insula, respectively, may represent neural correlates of impaired clinical insight in schizophrenia spectrum disorders, and is consistent with the literature attributing impaired insight to left hemisphere dominance. Increased connectivity in the DAN with the IFC and ACC in relation to cognitive insight may facilitate enhanced mental flexibility in this sample. PMID:25458571

Finding the rhythm of sudden cardiac death: new opportunities using induced pluripotent stem cell-derived cardiomyocytes.

PubMed

Sallam, Karim; Li, Yingxin; Sager, Philip T; Houser, Steven R; Wu, Joseph C

2015-06-05

Sudden cardiac death is a common cause of death in patients with structural heart disease, genetic mutations, or acquired disorders affecting cardiac ion channels. A wide range of platforms exist to model and study disorders associated with sudden cardiac death. Human clinical studies are cumbersome and are thwarted by the extent of investigation that can be performed on human subjects. Animal models are limited by their degree of homology to human cardiac electrophysiology, including ion channel expression. Most commonly used cellular models are cellular transfection models, which are able to mimic the expression of a single-ion channel offering incomplete insight into changes of the action potential profile. Induced pluripotent stem cell-derived cardiomyocytes resemble, but are not identical, adult human cardiomyocytes and provide a new platform for studying arrhythmic disorders leading to sudden cardiac death. A variety of platforms exist to phenotype cellular models, including conventional and automated patch clamp, multielectrode array, and computational modeling. Induced pluripotent stem cell-derived cardiomyocytes have been used to study long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, hypertrophic cardiomyopathy, and other hereditary cardiac disorders. Although induced pluripotent stem cell-derived cardiomyocytes are distinct from adult cardiomyocytes, they provide a robust platform to advance the science and clinical care of sudden cardiac death. © 2015 American Heart Association, Inc.

Building clinical and organizational resilience to reconcile safety threats, tensions and trade-offs: insights from theory and evidence.

PubMed

Jeffs, Lianne; Tregunno, Deborah; MacMillan, Kathleen; Espin, Sherry

2009-01-01

Healthcare delivery settings are complex adaptive and tightly coupled, interrelated systems. Within the larger healthcare system, a key subsystem is the "clinical microsystem" level. It is at this level that clinicians are faced with high levels of uncertainty in their daily work - uncertainty that impacts the quality and safety of care that patients receive. The first aim of this paper is to enhance healthcare leaders' understanding of what is currently known about safety threats and strategies to manage the inherent tensions and trade-offs that occur in everyday practice. The second aim is to inform strategies that build clinical and organizational resilience through a multi-level framework derived from the collective theoretical and empirical work. Together, this information can strengthen safety practices throughout healthcare organizations.

Beyond the Laboratory, Into the Clinic: What Dogs with Disk Disease Have Taught Us About Photobiomodulation for Spinal Cord Injury.

PubMed

Robinson, Narda G

2017-11-01

For spinal-cord-injured (SCI) patients, integrative medicine approaches such as photomedicine and acupuncture can renew hope and offer previously unrecognized ways to help regain function and improve quality of life. By understanding the mechanisms of action that these two modalities share, practitioners can better target specific attributes of spinal cord pathophysiology that are limiting recovery. Naturally occurring intervertebral disk disease (IVDD) in dogs affords unparalleled translational opportunities to develop treatment strategies involving photobiomodulation and acupuncture. Insights derived through clinical trials of dogs with IVDD have the potential to raise the standard of care for both human and canine SCI patients.

Philosophers assess randomized clinical trials: the need for dialogue.

PubMed

Miké, V

1989-09-01

In recent years a growing number of professional philosophers have joined in the controversy over ethical aspects of randomized clinical trials (RCTs). Morally questionable in their utilitarian approach, RCTs are claimed by some to be in direct violation of the second form of Kant's Categorical Imperative. But the arguments used in these critiques at times derive from a lack of insight into basic statistical procedures and the realities of the biomedical research process. Presented to physicians and other nonspecialists, including the lay public, such distortions can be harmful. Given the great complexity of statistical methodology and the anomalous nature of concepts of evidence, more sustained input into the interdisciplinary dialogue is needed from the statistical profession.

Prioritizing therapeutic targets using patient-derived xenograft models

PubMed Central

Lodhia, K.A; Hadley, A; Haluska, P; Scott, C.L

2015-01-01

Effective systemic treatment of cancer relies on the delivery of agents with optimal therapeutic potential. The molecular age of medicine has provided genomic tools that can identify a large number of potential therapeutic targets in individual patients, heralding the promise of personalized treatment. However, determining which potential targets actually drive tumor growth and should be prioritized for therapy is challenging. Indeed, reliable molecular matches of target and therapeutic agent have been stringently validated in the clinic for only a small number of targets. Patient-derived xenografts (PDX) are tumor models developed in immunocompromised mice using tumor procured directly from the patient. As patient surrogates, PDX models represent a powerful tool for addressing individualized therapy. Challenges include humanizing the immune system of PDX models and ensuring high quality molecular annotation, in order to maximise insights for the clinic. Importantly, PDX can be sampled repeatedly and in parallel, to reveal clonal evolution, which may predict mechanisms of drug resistance and inform therapeutic strategy design. PMID:25783201

Stem Cell-Derived Exosome in Cardiovascular Diseases: Macro Roles of Micro Particles.

PubMed

Yuan, Ye; Du, Weijie; Liu, Jiaqi; Ma, Wenya; Zhang, Lai; Du, Zhimin; Cai, Benzhi

2018-01-01

The stem cell-based therapy has emerged as the promising therapeutic strategies for cardiovascular diseases (CVDs). Recently, increasing evidence suggest stem cell-derived active exosomes are important communicators among cells in the heart via delivering specific substances to the adjacent/distant target cells. These exosomes and their contents such as certain proteins, miRNAs and lncRNAs exhibit huge beneficial effects on preventing heart damage and promoting cardiac repair. More importantly, stem cell-derived exosomes are more effective and safer than stem cell transplantation. Therefore, administration of stem cell-derived exosomes will expectantly be an alternative stem cell-based therapy for the treatment of CVDs. Furthermore, modification of stem cell-derived exosomes or artificial synthesis of exosomes will be the new therapeutic tools for CVDs in the future. In addition, stem cell-derived exosomes also have been implicated in the diagnosis and prognosis of CVDs. In this review, we summarize the current advances of stem cell-derived exosome-based treatment and prognosis for CVDs, including their potential benefits, underlying mechanisms and limitations, which will provide novel insights of exosomes as a new tool in clinical therapeutic translation in the future.

Left ventricular volume analysis as a basic tool to describe cardiac function.

PubMed

Kerkhof, Peter L M; Kuznetsova, Tatiana; Ali, Rania; Handly, Neal

2018-03-01

The heart is often regarded as a compression pump. Therefore, determination of pressure and volume is essential for cardiac function analysis. Traditionally, ventricular performance was described in terms of the Starling curve, i.e., output related to input. This view is based on two variables (namely, stroke volume and end-diastolic volume), often studied in the isolated (i.e., denervated) heart, and has dominated the interpretation of cardiac mechanics over the last century. The ratio of the prevailing coordinates within that paradigm is termed ejection fraction (EF), which is the popular metric routinely used in the clinic. Here we present an insightful alternative approach while describing volume regulation by relating end-systolic volume (ESV) to end-diastolic volume. This route obviates the undesired use of metrics derived from differences or ratios, as employed in previous models. We illustrate basic principles concerning ventricular volume regulation by data obtained from intact animal experiments and collected in healthy humans. Special attention is given to sex-specific differences. The method can be applied to the dynamics of a single heart and to an ensemble of individuals. Group analysis allows for stratification regarding sex, age, medication, and additional clinically relevant covariates. A straightforward procedure derives the relationship between EF and ESV and describes myocardial oxygen consumption in terms of ESV. This representation enhances insight and reduces the impact of the metric EF, in favor of the end-systolic elastance concept advanced 4 decades ago.

Comparison of insight and clinical variables in homeless and non-homeless psychiatric inpatients in China.

PubMed

Fu, Yan-Nan; Cao, Xiao-Lan; Hou, Cai-Lan; Ng, Chee H; Ungvari, Gabor S; Chiu, Helen F K; Lin, Yong-Qiang; Wang, Lihui; Zheng, Xiaocong; Jia, Fu-Jun; Xiang, Yu-Tao

2017-09-01

There are no published data on insight in homeless patients with psychiatric disorders in China. This study examined insight in homeless and non-homeless Chinese psychiatric inpatients in relation to demographic and clinical variables. A total of 278 homeless and 222 non-homeless inpatients matched in age and gender were included in the study. Demographic and clinical characteristics were collected based on a review of medical charts and a clinical interview with standardized instruments. Insight was evaluated with the Insight and Treatment Attitudes Questionnaire. Altogether 20.5% of homeless inpatients and 43.7% of the non-homeless controls had good insight. Compared with homeless inpatients with impaired insight, homeless inpatients with good insight had higher physical quality of life, longer duration of illness and less severe positive and negative symptoms. Impaired insight appeared more common in homeless psychiatric inpatients in China. Further studies should address the need for effective therapeutic interventions that promote homeless patients' insight. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Big Data Analytics for Genomic Medicine

PubMed Central

He, Karen Y.; Ge, Dongliang; He, Max M.

2017-01-01

Genomic medicine attempts to build individualized strategies for diagnostic or therapeutic decision-making by utilizing patients’ genomic information. Big Data analytics uncovers hidden patterns, unknown correlations, and other insights through examining large-scale various data sets. While integration and manipulation of diverse genomic data and comprehensive electronic health records (EHRs) on a Big Data infrastructure exhibit challenges, they also provide a feasible opportunity to develop an efficient and effective approach to identify clinically actionable genetic variants for individualized diagnosis and therapy. In this paper, we review the challenges of manipulating large-scale next-generation sequencing (NGS) data and diverse clinical data derived from the EHRs for genomic medicine. We introduce possible solutions for different challenges in manipulating, managing, and analyzing genomic and clinical data to implement genomic medicine. Additionally, we also present a practical Big Data toolset for identifying clinically actionable genetic variants using high-throughput NGS data and EHRs. PMID:28212287

Big Data Analytics for Genomic Medicine.

PubMed

He, Karen Y; Ge, Dongliang; He, Max M

2017-02-15

Genomic medicine attempts to build individualized strategies for diagnostic or therapeutic decision-making by utilizing patients' genomic information. Big Data analytics uncovers hidden patterns, unknown correlations, and other insights through examining large-scale various data sets. While integration and manipulation of diverse genomic data and comprehensive electronic health records (EHRs) on a Big Data infrastructure exhibit challenges, they also provide a feasible opportunity to develop an efficient and effective approach to identify clinically actionable genetic variants for individualized diagnosis and therapy. In this paper, we review the challenges of manipulating large-scale next-generation sequencing (NGS) data and diverse clinical data derived from the EHRs for genomic medicine. We introduce possible solutions for different challenges in manipulating, managing, and analyzing genomic and clinical data to implement genomic medicine. Additionally, we also present a practical Big Data toolset for identifying clinically actionable genetic variants using high-throughput NGS data and EHRs.

Insight and illness perception in Mexican patients with psychosis.

PubMed

Gómez-de-Regil, Lizzette

2015-03-01

Insight and illness perception are two concepts of interest in the study of factors related to clinical outcome in patients with psychosis. Insight implies a risk of emotional distress for the patient. Illness perceptions, regardless of their accuracy, might be favorable or not to illness. Literature provides evidence of significant correlates of these factors with clinical outcome, but they are rarely included in a single study. 1) assessing insight and illness perception in a sample of Mexican patients who have experienced psychosis and, 2) analyzing how insight and illness perception relate to each other and how they relate to clinical status (i.e., positive, negative, and general psychopathology, depression, and anxiety). Sixty-one participants (55.7% females) were recruited from a public psychiatric hospital; insight and illness perceptions were assessed with the SUMD and the Brief-IPQ, respectively. Clinical status was assessed with the PANSS, CDS and BAI scales. Participants showed good insight, favorable illness perceptions for the cognitive and comprehension dimensions, but unfavorable for the emotional dimension. Clinical status of sample was characterized by mild symptoms. Poor insight related to positive symptoms and general psychopathology. Cognitive and emotional perceptions of illness were significantly associated to most clinical status parameters, whereas comprehension showed no significant results. The study not only replicates the significant association on insight and illness perception with clinical outcome, but shows how their patterns of interactions are different, reinforcing the idea that they are two distinct factors worthy of being habitually acknowledged in research and clinical practice.

An Analysis of a Digital Variant of the Trail Making Test Using Machine Learning Techniques

PubMed Central

Dahmen, Jessamyn; Cook, Diane; Fellows, Robert; Schmitter-Edgecombe, Maureen

2017-01-01

BACKGROUND The goal of this work is to develop a digital version of a standard cognitive assessment, the Trail Making Test (TMT), and assess its utility. OBJECTIVE This paper introduces a novel digital version of the TMT and introduces a machine learning based approach to assess its capabilities. METHODS Using digital Trail Making Test (dTMT) data collected from (N=54) older adult participants as feature sets, we use machine learning techniques to analyze the utility of the dTMT and evaluate the insights provided by the digital features. RESULTS Predicted TMT scores correlate well with clinical digital test scores (r=0.98) and paper time to completion scores (r=0.65). Predicted TICS exhibited a small correlation with clinically-derived TICS scores (r=0.12 Part A, r=0.10 Part B). Predicted FAB scores exhibited a small correlation with clinically-derived FAB scores (r=0.13 Part A, r=0.29 for Part B). Digitally-derived features were also used to predict diagnosis (AUC of 0.65). CONCLUSION Our findings indicate that the dTMT is capable of measuring the same aspects of cognition as the paper-based TMT. Furthermore, the dTMT’s additional data may be able to help monitor other cognitive processes not captured by the paper-based TMT alone. PMID:27886019

Effects of sub-clinical psychosis and cognitive insight on psychological well-being: a structural equation model.

PubMed

Weintraub, Marc J; Weisman de Mamani, Amy

2015-03-30

Psychological well-being has been widely researched along the psychosis spectrum, and increased psychotic symptoms are generally associated with worse well-being. Additionally, the construct of insight has been extensively studied in schizophrenia. While having greater insight has many benefits for those with schizophrenia, a paradox exists in which greater insight is also associated with poorer psychological well-being. However, it is unclear whether the link between insight and poor well-being occurs only once serious psychopathology has been established, or whether this is a more universal process seen even at lower levels on the psychosis spectrum. We used a structural modeling approach in an ethnically diverse, non-clinical sample of 420 undergraduates to evaluate the association between sub-clinical psychosis, cognitive insight and psychological well-being. As hypothesized, results indicated that sub-clinical psychotic symptoms were negatively associated with psychological well-being. The insight paradox was also substantiated, as greater cognitive insight was associated with worse psychological well-being. However, cognitive insight did not moderate the association between symptoms and well-being. The link between sub-clinical psychotic symptoms and psychological well-being as well as the insight paradox appears to emerge even before reaching threshold for a psychotic disorder. Research and clinical implications are discussed. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Median regression spline modeling of longitudinal FEV1 measurements in cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) patients.

PubMed

Conrad, Douglas J; Bailey, Barbara A; Hardie, Jon A; Bakke, Per S; Eagan, Tomas M L; Aarli, Bernt B

2017-01-01

Clinical phenotyping, therapeutic investigations as well as genomic, airway secretion metabolomic and metagenomic investigations can benefit from robust, nonlinear modeling of FEV1 in individual subjects. We demonstrate the utility of measuring FEV1 dynamics in representative cystic fibrosis (CF) and chronic obstructive pulmonary disease (COPD) populations. Individual FEV1 data from CF and COPD subjects were modeled by estimating median regression splines and their predicted first and second derivatives. Classes were created from variables that capture the dynamics of these curves in both cohorts. Nine FEV1 dynamic variables were identified from the splines and their predicted derivatives in individuals with CF (n = 177) and COPD (n = 374). Three FEV1 dynamic classes (i.e. stable, intermediate and hypervariable) were generated and described using these variables from both cohorts. In the CF cohort, the FEV1 hypervariable class (HV) was associated with a clinically unstable, female-dominated phenotypes while stable FEV1 class (S) individuals were highly associated with the male-dominated milder clinical phenotype. In the COPD cohort, associations were found between the FEV1 dynamic classes, the COPD GOLD grades, with exacerbation frequency and symptoms. Nonlinear modeling of FEV1 with splines provides new insights and is useful in characterizing CF and COPD clinical phenotypes.

AllergoOncology - the impact of allergy in oncology: EAACI position paper.

PubMed

Jensen-Jarolim, E; Bax, H J; Bianchini, R; Capron, M; Corrigan, C; Castells, M; Dombrowicz, D; Daniels-Wells, T R; Fazekas, J; Fiebiger, E; Gatault, S; Gould, H J; Janda, J; Josephs, D H; Karagiannis, P; Levi-Schaffer, F; Meshcheryakova, A; Mechtcheriakova, D; Mekori, Y; Mungenast, F; Nigro, E A; Penichet, M L; Redegeld, F; Saul, L; Singer, J; Spicer, J F; Siccardi, A G; Spillner, E; Turner, M C; Untersmayr, E; Vangelista, L; Karagiannis, S N

2017-06-01

Th2 immunity and allergic immune surveillance play critical roles in host responses to pathogens, parasites and allergens. Numerous studies have reported significant links between Th2 responses and cancer, including insights into the functions of IgE antibodies and associated effector cells in both antitumour immune surveillance and therapy. The interdisciplinary field of AllergoOncology was given Task Force status by the European Academy of Allergy and Clinical Immunology in 2014. Affiliated expert groups focus on the interface between allergic responses and cancer, applied to immune surveillance, immunomodulation and the functions of IgE-mediated immune responses against cancer, to derive novel insights into more effective treatments. Coincident with rapid expansion in clinical application of cancer immunotherapies, here we review the current state-of-the-art and future translational opportunities, as well as challenges in this relatively new field. Recent developments include improved understanding of Th2 antibodies, intratumoral innate allergy effector cells and mediators, IgE-mediated tumour antigen cross-presentation by dendritic cells, as well as immunotherapeutic strategies such as vaccines and recombinant antibodies, and finally, the management of allergy in daily clinical oncology. Shedding light on the crosstalk between allergic response and cancer is paving the way for new avenues of treatment. © 2016 John Wiley & Sons A/S . Published by John Wiley & Sons Ltd.

AllergoOncology - The impact of Allergy in Oncology. EAACI Position Paper

PubMed Central

Jensen-Jarolim, E; Bax, HJ; Bianchini, R; Capron, M; Corrigan, C; Castells, M; Dombrowicz, D; Daniels-Wells, TR; Fazekas, J; Fiebiger, E; Gatault, S; Gould, HJ; Janda, J; Josephs, DH; Karagiannis, P; Levi-Schaffer, F; Meshcheryakova, A; Mechtcheriakova, D; Mekori, Y; Mungenast, F; Nigro, EA; Penichet, ML; Redegeld, F; Saul, L; Singer, J; Spicer, JF; Siccardi, AG; Spillner, E; Turner, MC; Untersmayr, E; Vangelista, L; Karagiannis, SN

2017-01-01

Th2 immunity and allergic immune surveillance play critical roles in host responses to pathogens, parasites and allergens. Numerous studies have reported significant links between Th2 responses and cancer, including insights into the functions of IgE antibodies and associated effector cells in both anti-tumour immune surveillance and therapy. The interdisciplinary field of AllergoOncology was given Task Force status by the European Academy of Allergy and Clinical Immunology in 2014. Affiliated expert groups focus on the interface between allergic responses and cancer, applied to immune surveillance, immunomodulation and the functions of IgE-mediated immune responses against cancer, to derive novel insights into more effective treatments. Co-incident with rapid expansion in clinical application of cancer immunotherapies, here we review the current state-of-the-art and future translational opportunities, as well as challenges in this relatively new field. Recent developments include improved understanding of Th2 antibodies, intra-tumoural innate allergy effector cells and mediators, IgE-mediated tumour antigen cross-presentation by dendritic cells, as well as immunotherapeutic strategies such as vaccines and recombinant antibodies, and finally, the management of allergy in daily clinical oncology. Shedding light on the cross-talk between allergic response and cancer is paving the way for new avenues of treatment. PMID:28032353

Pathophysiology and animal modeling of underactive bladder

PubMed Central

Tyagi, Pradeep; Smith, Phillip P.; Kuchel, George A.; de Groat, William C.; Birder, Lori A.; Chermansky, Christopher J.; Adam, Rosalyn M.; Tse, Vincent; Chancellor, Michael B.; Yoshimura, Naoki

2015-01-01

While the symptomology of underactive bladder (UAB) may imply a primary dysfunction of the detrusor muscle, insights into pathophysiology indicate that both myogenic and neurogenic mechanisms need to be considered. Due to lack of proper animal models, the current understanding of the UAB pathophysiology is limited, and much of what is known about the clinical etiology of the condition has been derived from epidemiological data. We hereby review current state of the art in the understanding of the pathophysiology of and animal models used to study the UAB. PMID:25238890

Cinnamic Acid and Its Derivatives: Mechanisms for Prevention and Management of Diabetes and Its Complications.

PubMed

Adisakwattana, Sirichai

2017-02-21

With recent insight into the development of dietary supplements and functional foods, search of effective phytochemical compounds and their mechanisms involved in prevention and management of diabetes and its complications are now being assessed. Cinnamic acid and its derivatives occur naturally in high levels of plant-based foods. Among various biological activities, cinnamic acid and its derivatives are associated with a beneficial influence on diabetes and its complications. The aim of the review is to summarize the potential mechanisms of these compounds for prevention and management of diabetes and its complications. Based on several in vitro studies and animal models, cinnamic acid and its derivatives act on different mechanism of actions, including stimulation of insulin secretion, improvement of pancreatic β-cell functionality, inhibition of hepatic gluconeogenesis, enhanced glucose uptake, increased insulin signaling pathway, delay of carbohydrate digestion and glucose absorption, and inhibition of protein glycation and insulin fibrillation. However, due to the limited intestinal absorption being a result of low bioavailability of cinnamic acid and its derivatives, current improvement efforts with entrapping into solid and liquid particles are highlighted. Further human clinical studies are needed to clarify the effects of cinnamic acid and its derivatives in diabetic patients.

Cinnamic Acid and Its Derivatives: Mechanisms for Prevention and Management of Diabetes and Its Complications

PubMed Central

Adisakwattana, Sirichai

2017-01-01

With recent insight into the development of dietary supplements and functional foods, search of effective phytochemical compounds and their mechanisms involved in prevention and management of diabetes and its complications are now being assessed. Cinnamic acid and its derivatives occur naturally in high levels of plant-based foods. Among various biological activities, cinnamic acid and its derivatives are associated with a beneficial influence on diabetes and its complications. The aim of the review is to summarize the potential mechanisms of these compounds for prevention and management of diabetes and its complications. Based on several in vitro studies and animal models, cinnamic acid and its derivatives act on different mechanism of actions, including stimulation of insulin secretion, improvement of pancreatic β-cell functionality, inhibition of hepatic gluconeogenesis, enhanced glucose uptake, increased insulin signaling pathway, delay of carbohydrate digestion and glucose absorption, and inhibition of protein glycation and insulin fibrillation. However, due to the limited intestinal absorption being a result of low bioavailability of cinnamic acid and its derivatives, current improvement efforts with entrapping into solid and liquid particles are highlighted. Further human clinical studies are needed to clarify the effects of cinnamic acid and its derivatives in diabetic patients. PMID:28230764

Clinical correlates of loss of insight in bipolar depression.

PubMed

Silva, Rafael de Assis da; Mograbi, Daniel C; Camelo, Evelyn V M; Santana, Cristina M T; Landeira-Fernandez, Jesus; Cheniaux, Elie

2017-01-01

Affective state may influence insight, especially regarding mania. Nevertheless, studies have so far suggested that depression seems not to significantly impair insight. To the best of our knowledge, this study pioneers the evaluation of how insight variations in bipolar depression correlate with clinical variables. A group of 165 bipolar patients, 52 of whom had depressive episodes according to DSM-5 criteria, were followed during a year. All patients underwent clinical assessment, and insight was evaluated through the Insight Scale for Affective Disorders (ISAD). Repeated-measures ANOVA was calculated comparing scores on the four ISAD factors (insight into symptoms, the condition itself, self-esteem and social relationships) in order to investigate differences in insight according to different objects. Correlational analysis explored which clinical symptoms were linked to reduced insight. Worse total insight correlated with suicide attempt/ideation and fewer subsyndromal manic symptoms such as mood elevation, increased energy and sexual interest. Worse self-esteem insight was associated with not only suicide ideation/attempt but also with activity reduction and psychomotor retardation. Worse symptom insight also correlated with psychomotor retardation. Better insight into having an affective disorder was associated with more intense hypochondria symptoms. Finally, worse insight into having an illness was associated with psychotic episodes. Our study found that symptoms other than psychosis - suicide ideation, psychomotor retardation and reduction of activity and work - correlate with insight impairment in bipolar depression.

A prospective study of the trajectories of clinical insight, affective symptoms, and cognitive ability in bipolar disorder

PubMed Central

Depp, Colin A.; Harmell, Alexandrea L.; Savla, Gauri N.; Mausbach, Brent T.; Jeste, Dilip V.; Palmer, Barton W.

2014-01-01

Background Clinical insight in bipolar disorder is associated with treatment adherence and psychosocial outcome. The short-term dynamics of clinical insight in relationship to symptoms and cognitive abilities are unknown. Methods In a prospective observational study, a total of 106 outpatients with bipolar disorder I or II were assessed at baseline, 6 weeks, 12 weeks, and 26 weeks. Participants were administered a comprehensive neuropsychological battery, clinical ratings of manic and depressive symptom severity, and self-reported clinical insight. Lagged correlations and linear mixed-effects models were used to determine the temporal associations between symptoms and insight, as well as the moderating influence of global cognitive abilities. Results At baseline, insight was modestly correlated with severity of manic symptoms, but not with depressive symptoms or cognitive abilities. Insight and depressive symptoms fluctuated to approximately the same extent over time. Both lagged correlations and mixed effects models with lagged effects indicated that the severity of manic symptoms predicted worse insight at later assessments, whereas the converse was not significant. There were no direct or moderating influences of global cognitive abilities. Limitations Our sample size was modest, and included relatively psychiatrically stable outpatients, followed for a six month period. Our results may not generalize to acutely symptomatic patients followed over a longer period. Conclusions Clinical insight varies substantially over time within patients with bipolar disorder. Impaired insight in bipolar disorder is more likely to follow than to precede manic symptoms. PMID:24200153

The scent of disease: volatile organic compounds of the human body related to disease and disorder.

PubMed

Shirasu, Mika; Touhara, Kazushige

2011-09-01

Hundreds of volatile organic compounds (VOCs) are emitted from the human body, and the components of VOCs usually reflect the metabolic condition of an individual. Therefore, contracting an infectious or metabolic disease often results in a change in body odour. Recent progresses in analytical techniques allow rapid analyses of VOCs derived from breath, blood, skin and urine. Disease-specific VOCs can be used as diagnostic olfactory biomarkers of infectious diseases, metabolic diseases, genetic disorders and other kinds of diseases. Elucidation of pathophysiological mechanisms underlying production of disease-specific VOCs may provide novel insights into therapeutic approaches for treatments for various diseases. This review summarizes the current knowledge on chemical and clinical aspects of body-derived VOCs, and provides a brief outlook at the future of olfactory diagnosis.

Association between insight, cognitive insight, positive symptoms and violence in patients with schizophrenia.

PubMed

Ekinci, Okan; Ekinci, Asli

2013-04-01

Violence is a significant clinical and public concern and is a frequent occurrence in patients with schizophrenia. The relationship between insight and violence remains controversial. In addition, there is a lack of research on insight, cognitive insight, demographic and psychopathologic variables in violent versus nonviolent schizophrenia patients. We aimed to compare insight, cognitive insight, psychopathological and demographic variables in violent and nonviolent subjects suffering from schizophrenia. In addition, we aimed to determine the demographic and clinical predictors of violent behaviour in patients with schizophrenia. We recruited 133 schizophrenic patients without concomitant substance abuse or axis II disorder. Diagnoses were based on the SCID-I and SCID-II. Violent behaviours were assessed using the Overt Aggression Scale. Insight and cognitive insight were assessed with the Scale to Assess Unawareness of Mental Disorder and the Beck Cognitive Insight Scale, respectively. We compared 47 patients with violent schizophrenia with 86 nonviolent patients. Non-violent patients had more severe depression, lower scores on positive symptoms, better clinical insight, more self-reflectivity and higher R-C index scores than did violent patients. In addition, history of violence, lower self-reflectiveness, worse clinical insight and delusion severity were significant predictors of violence in schizophrenia. The present study suggests that the inclusion of insight and cognitive insight may increase the prediction of violence in this population. In addition, clinicians should consider using non-pharmacological techniques that are based on cognitive behaviour therapy and enhance insight, particularly cognitive insight, among patients with schizophrenia who exhibit violent behaviour.

Are privacy-enhancing technologies for genomic data ready for the clinic? A survey of medical experts of the Swiss HIV Cohort Study.

PubMed

Raisaro, Jean-Louis; McLaren, Paul J; Fellay, Jacques; Cavassini, Matthias; Klersy, Catherine; Hubaux, Jean-Pierre

2018-03-01

Protecting patient privacy is a major obstacle for the implementation of genomic-based medicine. Emerging privacy-enhancing technologies can become key enablers for managing sensitive genetic data. We studied physicians' attitude toward this kind of technology in order to derive insights that might foster their future adoption for clinical care. We conducted a questionnaire-based survey among 55 physicians of the Swiss HIV Cohort Study who tested the first implementation of a privacy-preserving model for delivering genomic test results. We evaluated their feedback on three different aspects of our model: clinical utility, ability to address privacy concerns and system usability. 38/55 (69%) physicians participated in the study. Two thirds of them acknowledged genetic privacy as a key aspect that needs to be protected to help building patient trust and deploy new-generation medical information systems. All of them successfully used the tool for evaluating their patients' pharmacogenomics risk and 90% were happy with the user experience and the efficiency of the tool. Only 8% of physicians were unsatisfied with the level of information and wanted to have access to the patient's actual DNA sequence. This survey, although limited in size, represents the first evaluation of privacy-preserving models for genomic-based medicine. It has allowed us to derive unique insights that will improve the design of these new systems in the future. In particular, we have observed that a clinical information system that uses homomorphic encryption to provide clinicians with risk information based on sensitive genetic test results can offer information that clinicians feel sufficient for their needs and appropriately respectful of patients' privacy. The ability of this kind of systems to ensure strong security and privacy guarantees and to provide some analytics on encrypted data has been assessed as a key enabler for the management of sensitive medical information in the near future. Providing clinically relevant information to physicians while protecting patients' privacy in order to comply with regulations is crucial for the widespread use of these new technologies. Copyright © 2017. Published by Elsevier Inc.

How self-reflection and self-certainty are related to neurocognitive functioning: an examination of cognitive insight in bipolar disorder.

PubMed

Van Camp, L S C; Oldenburg, J F E; Sabbe, B G C

2016-01-01

The pattern of associations between clinical insight, cognitive insight, and neurocognitive functioning was assessed in bipolar disorder patients. Data from 42 bipolar disorder patients were examined. Cognitive insight was measured using the Beck Cognitive Insight Scale (BCIS). The BCIS is a 15-item self-report instrument consisting of two subscales, self-reflectiveness and self-certainty. Clinical insight was measured by the use of the item G12 of the Positive and Negative Syndrome Scale. Neurocognitive functioning was assessed using the International Society for Bipolar Disorders-Battery for Assessment of Neurocognition. Correlation analyses revealed significant positive associations between self-reflectiveness and speed of processing, attention, working memory, visual learning, and reasoning and problem solving. The subscale self-certainty was negatively correlated to working memory, however, this correlation disappeared when we controlled for confounding variables. No correlations between clinical insight and neurocognition were found. In addition, there was no association between cognitive insight and clinical insight. Better neurocognitive functioning was more related to higher levels of self-reflectiveness than to diminished self-certainty.

An insight of traditional plasmid curing in Vibrio species

PubMed Central

Letchumanan, Vengadesh; Chan, Kok-Gan; Lee, Learn-Han

2015-01-01

As the causative agent of foodborne related illness, Vibrio species causes a huge impact on the public health and management. Vibrio species is often associated with seafood as the latter plays a role as a vehicle to transmit bacterial infections. Hence, antibiotics are used not to promote growth but rather to prevent and treat bacterial infections. The extensive use of antibiotics in the aquaculture industry and environment has led to the emerging of antibiotic resistant strains. This phenomenon has triggered an alarming public health concern due to the increase number of pathogenic Vibrio strains that are resistant to clinically used antibiotics and is found in the environment. Antibiotic resistance and the genes location in the strains can be detected through plasmid curing assay. The results derived from plasmid curing assay is fast, cost effective, sufficient in providing insights, and influence the antibiotic management policies in the aquaculture industry. This presentation aims in discussing and providing insights on various curing agents in Vibrio species. To our best of knowledge, this is a first review written discussing on plasmid curing in Vibrio species. PMID:26347714

Bridging different perspectives of the physiological and mathematical disciplines.

PubMed

Batzel, Jerry Joseph; Hinghofer-Szalkay, Helmut; Kappel, Franz; Schneditz, Daniel; Kenner, Thomas; Goswami, Nandu

2012-12-01

The goal of this report is to discuss educational approaches for bridging the different perspectives of the physiological and mathematical disciplines. These approaches can enhance the learning experience for physiology, medical, and mathematics students and simultaneously act to stimulate mathematical/physiological/clinical interdisciplinary research. While physiology education incorporates mathematics, via equations and formulas, it does not typically provide a foundation for interdisciplinary research linking mathematics and physiology. Here, we provide insights and ideas derived from interdisciplinary seminars involving mathematicians and physiologists that have been conducted over the last decade. The approaches described here can be used as templates for giving physiology and medical students insights into how sophisticated tools from mathematics can be applied and how the disciplines of mathematics and physiology can be integrated in research, thereby fostering a foundation for interdisciplinary collaboration. These templates are equally applicable to linking mathematical methods with other life and health sciences in the educational process.

Does self reflection and insight correlate with academic performance in medical students?

PubMed

Carr, Sandra E; Johnson, Paula H

2013-08-23

Medical students in academic difficulty are often described as lacking insight. The Self Reflection and Insight Scale (SRIS) is a tool for measuring insight which has been validated in medical students. We investigated whether self reflection and insight scores correlate with academic performance in Year 4 medical students from a six year undergraduate medical degree, and whether self reflection and insight changes after one year of clinical training. Self reflection and insight scores were measured in 162 students at the start of Year 4 at the University of Western Australia. Performance in end of year written and clinical exams was monitored and correlated with SRIS. Seventy of the students were surveyed again at the start of Year 5 to see if scores changed or were stable after one year of full time clinical training. We found no correlation between self reflection or insight and academic performance in written and clinical exams. There was a significant increase in recognition of the need for self reflection in Year 5 compared with Year 4. While no correlation was found between this measure of self reflection and insight with academic performance, there was an increase in students' recognition of the need for reflection after one year of clinical studies. This study is a valuable first step towards a potentially exciting research domain and warrants further longitudinal evaluation with larger cohorts of students using additional measures of achievement.

Depression in schizophrenia: the influence of the different dimensions of insight.

PubMed

Misdrahi, David; Denard, Sophie; Swendsen, Joel; Jaussent, Isabelle; Courtet, Philippe

2014-04-30

Improving insight in patients with schizophrenia appears necessary to enhance medication adherence and clinical outcome, but in some patients acquiring insight can paradoxically increase hopelessness, depression and suicidal behavior. The aim of this study is to explore the association of two dimensions of insight (cognitive and clinical) with depression, hopelessness and clinical variables in patients with psychosis. Using a cross-sectional design, 61 remitted outpatients meeting DSM-IV criteria for schizophrenia or schizoaffective disorders were included. Insight was assessed using the "Scale to Assess Unawareness of Mental Disorder" (SUMD), the PANSS-item G12 and the Beck Cognitive Insight Scale (BCIS). Overall, 41.2% of the sample had a history of suicide attempts. Patients in the high clinical insight group had significantly higher depression scores, higher hopelessness scores, greater histories of suicide attempts and were more likely to have received psychoeducation. Compared to patients with low cognitive insight, those with high overall cognitive insight were significantly more depressed and had more often received psychoeducation. Greater insight may have negative consequences in terms of depressive symptoms and therefore presents a challenge to clinicians in assessing the individual risks and benefits of strategies intended to enhance awareness of mental disorder. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Derivative component analysis for mass spectral serum proteomic profiles.

PubMed

Han, Henry

2014-01-01

As a promising way to transform medicine, mass spectrometry based proteomics technologies have seen a great progress in identifying disease biomarkers for clinical diagnosis and prognosis. However, there is a lack of effective feature selection methods that are able to capture essential data behaviors to achieve clinical level disease diagnosis. Moreover, it faces a challenge from data reproducibility, which means that no two independent studies have been found to produce same proteomic patterns. Such reproducibility issue causes the identified biomarker patterns to lose repeatability and prevents it from real clinical usage. In this work, we propose a novel machine-learning algorithm: derivative component analysis (DCA) for high-dimensional mass spectral proteomic profiles. As an implicit feature selection algorithm, derivative component analysis examines input proteomics data in a multi-resolution approach by seeking its derivatives to capture latent data characteristics and conduct de-noising. We further demonstrate DCA's advantages in disease diagnosis by viewing input proteomics data as a profile biomarker via integrating it with support vector machines to tackle the reproducibility issue, besides comparing it with state-of-the-art peers. Our results show that high-dimensional proteomics data are actually linearly separable under proposed derivative component analysis (DCA). As a novel multi-resolution feature selection algorithm, DCA not only overcomes the weakness of the traditional methods in subtle data behavior discovery, but also suggests an effective resolution to overcoming proteomics data's reproducibility problem and provides new techniques and insights in translational bioinformatics and machine learning. The DCA-based profile biomarker diagnosis makes clinical level diagnostic performances reproducible across different proteomic data, which is more robust and systematic than the existing biomarker discovery based diagnosis. Our findings demonstrate the feasibility and power of the proposed DCA-based profile biomarker diagnosis in achieving high sensitivity and conquering the data reproducibility issue in serum proteomics. Furthermore, our proposed derivative component analysis suggests the subtle data characteristics gleaning and de-noising are essential in separating true signals from red herrings for high-dimensional proteomic profiles, which can be more important than the conventional feature selection or dimension reduction. In particular, our profile biomarker diagnosis can be generalized to other omics data for derivative component analysis (DCA)'s nature of generic data analysis.

Controversies in Cardiovascular Research: Induced pluripotent stem cell-derived cardiomyocytes – boutique science or valuable arrhythmia model?

PubMed Central

Knollmann, Björn C

2013-01-01

As part of the series on Controversies in Cardiovascular Research, the article reviews the strengths and limitations of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) as models of cardiac arrhythmias. Specifically, the article attempts to answer the following questions: Which clinical arrhythmias can be modeled by iPSC-CM? How well can iPSC-CM model adult ventricular myocytes? What are the strengths and limitations of published iPSC-CM arrhythmia models? What new mechanistic insight has been gained? What is the evidence that would support using iPSC-CM to personalize anti-arrhythmic drug therapy? The review also discusses the pros and cons of using the iPSC-CM technology for modeling specific genetic arrhythmia disorders such as long QT syndrome, Brugada Syndrome or Catecholaminergic Polymorphic Ventricular Tachycardia. PMID:23569106

Voxel-based magnetic resonance imaging investigation of poor and preserved clinical insight in people with schizophrenia.

PubMed

Sapara, Adegboyega; Ffytche, Dominic H; Cooke, Michael A; Williams, Steven Cr; Kumari, Veena

2016-09-22

To define regional grey-matter abnormalities in schizophrenia patients with poor insight (Insight(-)), relative to patients with preserved clinical insight (Insight(+)), and healthy controls. Forty stable schizophrenia outpatients (20 Insight(-) and 20 Insight(+)) and 20 healthy controls underwent whole brain magnetic resonance imaging (MRI). Insight in all patients was assessed using the Birchwood Insight Scale (BIS; a self-report measure). The two patient groups were pre-selected to match on most clinical and demographic parameters but, by design, they had markedly distinct BIS scores. Voxel-based morphometry employed in SPM8 was used to examine group differences in grey matter volumes across the whole brain. The three participant groups were comparable in age [F(2,57) = 0.34, P = 0.71] and the patient groups did not differ in age at illness onset [t(38) = 0.87, P = 0.39]. Insight(-) and Insight(+) patient groups also did not differ in symptoms on the Positive and Negative Syndromes scale (PANSS): Positive symptoms [t(38) = 0.58, P = 0.57], negative symptoms [t(38) = 0.61, P = 0.55], general psychopathology [t(38) = 1.30, P = 0.20] and total PANSS scores [t(38) = 0.21, P = 0.84]. The two patient groups, as expected, varied significantly in the level of BIS-assessed insight [t(38) = 12.11, P < 0.001]. MRI results revealed lower fronto-temporal, parahippocampal, occipital and cerebellar grey matter volumes in Insight(-) patients, relative to Insight(+) patients and healthy controls (for all clusters, family-wise error corrected P < 0.05). Insight(+) patient and healthy controls did not differ significantly (P > 0.20) from each other. Our findings demonstrate a clear association between poor clinical insight and smaller fronto-temporal, occipital and cerebellar grey matter volumes in stable long-term schizophrenia patients.

Clinical pitfalls in the diagnosis of ataque de nervios: a case study.

PubMed

Lizardi, Dana; Oquendo, Maria A; Graver, Ruth

2009-09-01

Ataque de nervios (attack of nerves) is an idiom of distress generally thought of in relation to Caribbean Hispanics. The following case study discusses the presentation of ataque de nervios in a Colombian female. This case study provides insight into a different presentation of ataque de nervios in a new population that clinicians should be aware of in order to ensure accurate diagnosis. Ataque de nervios is a distinct syndrome that does not fully correspond with any single DSM-IV diagnosis. However, there is overlap between symptoms in this condition and those in conventional clinical diagnoses. Common problems in deriving an accurate differential diagnosis are discussed. Implications for treatment are also reviewed, with an emphasis on a comprehensive approach to treatment that supports the client's norms and values.

Utilizing Big Data and Twitter to Discover Emergent Online Communities of Cannabis Users

PubMed Central

Baumgartner, Peter; Peiper, Nicholas

2017-01-01

Large shifts in medical, recreational, and illicit cannabis consumption in the United States have implications for personalizing treatment and prevention programs to a wide variety of populations. As such, considerable research has investigated clinical presentations of cannabis users in clinical and population-based samples. Studies leveraging big data, social media, and social network analysis have emerged as a promising mechanism to generate timely insights that can inform treatment and prevention research. This study extends a novel method called stochastic block modeling to derive communities of cannabis consumers as part of a complex social network on Twitter. A set of examples illustrate how this method can ascertain candidate samples of medical, recreational, and illicit cannabis users. Implications for research planning, intervention design, and public health surveillance are discussed. PMID:28615950

Understanding tumor heterogeneity as functional compartments - superorganisms revisited

PubMed Central

2011-01-01

Compelling evidence broadens our understanding of tumors as highly heterogeneous populations derived from one common progenitor. In this review we portray various stages of tumorigenesis, tumor progression, self-seeding and metastasis in analogy to the superorganisms of insect societies to exemplify the highly complex architecture of a neoplasm as a system of functional "castes." Accordingly, we propose a model in which clonal expansion and cumulative acquisition of genetic alterations produce tumor compartments each equipped with distinct traits and thus distinct functions that cooperate to establish clinically apparent tumors. This functional compartment model also suggests mechanisms for the self-construction of tumor stem cell niches. Thus, thinking of a tumor as a superorganism will provide systemic insight into its functional compartmentalization and may even have clinical implications. PMID:21619636

Structural basis for the inhibition of poly(ADP-ribose) polymerases 1 and 2 by BMN 673, a potent inhibitor derived from dihydropyridophthalazinone

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aoyagi-Scharber, Mika, E-mail: maoyagi@bmrn.com; Gardberg, Anna S.; Yip, Bryan K.

2014-08-29

BMN 673, a novel PARP1/2 inhibitor in clinical development with substantial tumor cytotoxicity, forms extensive hydrogen-bonding and π-stacking in the nicotinamide pocket, with its unique disubstituted scaffold extending towards the less conserved edges of the pocket. These interactions might provide structural insight into the ability of BMN 673 to both inhibit catalysis and affect DNA-binding activity. Poly(ADP-ribose) polymerases 1 and 2 (PARP1 and PARP2), which are involved in DNA damage response, are targets of anticancer therapeutics. BMN 673 is a novel PARP1/2 inhibitor with substantially increased PARP-mediated tumor cytotoxicity and is now in later-stage clinical development for BRCA-deficient breast cancers.more » In co-crystal structures, BMN 673 is anchored to the nicotinamide-binding pocket via an extensive network of hydrogen-bonding and π-stacking interactions, including those mediated by active-site water molecules. The novel di-branched scaffold of BMN 673 extends the binding interactions towards the outer edges of the pocket, which exhibit the least sequence homology among PARP enzymes. The crystallographic structural analyses reported here therefore not only provide critical insights into the molecular basis for the exceptionally high potency of the clinical development candidate BMN 673, but also new opportunities for increasing inhibitor selectivity.« less

Mechanisms, models and biomarkers in amyotrophic lateral sclerosis

PubMed Central

Turner, Martin R.; Bowser, Robert; Bruijn, Lucie; Dupuis, Luc; Ludolph, Albert; Mcgrath, Michael; Manfredi, Giovanni; Maragakis, Nicholas; Miller, Robert G.; Pullman, Seth L.; Rutkove, Seward B.; Shaw, Pamela J.; Shefner, Jeremy; Fischbeck, Kenneth H.

2014-01-01

The last 30 years have seen a major advance in the understanding of the clinical and pathological heterogeneity of amyotrophic lateral sclerosis (ALS), and its overlap with frontotemporal dementia. Multiple, seemingly disparate biochemical pathways converge on a common clinical syndrome characterized by progressive loss of upper and lower motor neurons. Pathogenic themes in ALS include excitotoxicity, oxidative stress, mitochondrial dysfunction, neuroinflammation, altered energy metabolism, and most recently RNA mis-processing. The transgenic rodent, overexpressing mutant superoxide dismutase-1, is now only one of several models of ALS pathogenesis. The nematode, fruit fly and zebrafish all offer fresh insight, and the development of induced pluripotent stem cell-derived motor neurons holds promise for the screening of candidate therapeutics. The lack of useful biomarkers in ALS contributes to diagnostic delay, and the inability to stratify patients by prognosis may be an important factor in the failure of therapeutic trials. Biomarkers sensitive to disease activity might lessen reliance on clinical measures and survival as trial endpoints and reduce study length. Emerging proteomic markers of neuronal loss and glial activity in cerebrospinal fluid, a cortical signature derived from advanced structural and functional MRI, and the development of more sensitive measurements of lower motor neuron physiology are leading a new phase of biomarker-driven therapeutic discovery. PMID:23678877

Steroid Sulfatase Inhibition by Aryl Sulfamates: Clinical Progress, Mechanism and Future Prospects.

PubMed

Potter, Barry V L

2018-04-04

Steroid sulfatase is an emerging drug target for the endocrine therapy of hormone-dependent diseases, catalyzing estrogen sulfate hydrolysis to estrogen. Drug discovery, developing the core aryl O-sulfamate pharmacophore, has led to steroidal and non-steroidal drugs entering numerous clinical trials, with promising results in oncology and women's health. Steroidal estrogen sulfamate derivatives were the first irreversible active-site-directed inhibitors and one was developed clinically as an oral estradiol pro-drug and for endometriosis applications. This review summarizes work leading to the therapeutic concept of sulfatase inhibition, clinical trials executed to date and new insights into the mechanism of inhibition of steroid sulfatase. To date the non-steroidal sulfatase inhibitor Irosustat has been evaluated clinically in breast cancer, alone and in combination, in endometrial cancer and in prostate cancer. The versatile core pharmacophore both imbues attractive pharmaceutical properties and functions via three distinct mechanisms of action, as a pro-drug, an enzyme active site-modifying motif, likely through direct sulfamoyl group transfer, and as a structural component augmenting activity, for example by enhancing interactions at the colchicine binding site of tubulin. Preliminary new structural data on the Pseudomonas aeruginosa arylsulfatase enzyme suggest two possible sulfamate-based adducts with active site hydrated formylglycine as candidates for the inhibition end product via sulfamoyl group transfer, and a speculative choice is suggested. The clinical status of sulfatase inhibition is surveyed and how it might develop in the future. Also discussed are dual-targeting approaches, development of 2-substituted steroidal sulfamates and nonsteroidal derivatives as multi-targeting agents for hormone-independent tumours with other emerging directions.

Does self reflection and insight correlate with academic performance in medical students?

PubMed Central

2013-01-01

Background Medical students in academic difficulty are often described as lacking insight. The Self Reflection and Insight Scale (SRIS) is a tool for measuring insight which has been validated in medical students. We investigated whether self reflection and insight scores correlate with academic performance in Year 4 medical students from a six year undergraduate medical degree, and whether self reflection and insight changes after one year of clinical training. Methods Self reflection and insight scores were measured in 162 students at the start of Year 4 at the University of Western Australia. Performance in end of year written and clinical exams was monitored and correlated with SRIS. Seventy of the students were surveyed again at the start of Year 5 to see if scores changed or were stable after one year of full time clinical training. Results We found no correlation between self reflection or insight and academic performance in written and clinical exams. There was a significant increase in recognition of the need for self reflection in Year 5 compared with Year 4. Conclusions While no correlation was found between this measure of self reflection and insight with academic performance, there was an increase in students’ recognition of the need for reflection after one year of clinical studies. This study is a valuable first step towards a potentially exciting research domain and warrants further longitudinal evaluation with larger cohorts of students using additional measures of achievement. PMID:23971859

Insight in Chinese schizophrenia patients: a 12-month follow-up.

PubMed

Wang, Y; Xiang, Y-T; Wang, C-Y; Chiu, H F K; Zhao, J-P; Chen, Q; Chan, S S M; Lee, E H M; Tang, W-K; Ungvari, G S

2011-11-01

This study aimed to assess insight in Chinese schizophrenia patients and to identify its relationship with socio-demographic and clinical factors, executive functions and quality of life (QOL). A cohort of 139 clinically stable schizophrenia patients was selected by consecutively screening patients diagnosed with schizophrenia who were attending the outpatient department of a university-affiliated psychiatric hospital in China. Participants' socio-demographic and clinical characteristics, including psychotic symptoms, depression and insight, as well as QOL and executive functions, were periodically assessed with standardized rating instruments. Patients received standard psychiatric care and were followed up for 1 year. Impaired insight was found to be common in stable Chinese schizophrenia patients (76.3%), with merely 5% showing improvement over the 1-year follow-up. Insight was inversely correlated with positive and negative symptoms at all but the 12-month assessment and with both the physical and mental components of QOL at baseline and the 12-month assessment. Insight was not associated with depressive symptoms or executive functions. Standard psychiatric care does not improve the level of insight in clinically stable Chinese schizophrenia outpatients, which warrants the introduction of specific therapeutic interventions that enhance insight. © 2011 Blackwell Publishing.

Anti-apoptotic effects of adipose-derived adherent stromal cells in mesenchymal stem cells exposed to oxidative stress.

PubMed

Shin, Sunhye; Choi, Jung-Won; Lim, Soyeon; Lee, Seahyoung; Jun, Eun-Young; Sun, Hyun-Min; Kim, Il-Kwon; Lee, Hoon-Bum; Kim, Sang Woo; Hwang, Ki-Chul

2018-06-19

Adipose-derived stromal vascular fractions (SVFs) are a heterogeneous collection of cells, and their regenerative modality has been applied in various animal experiments and clinical trials. Despite the attractive advantages of SVFs in clinical interventions, the recent status of clinical studies involving the application of SVFs in many diseases has not been fully evaluated. Mesenchymal stem cells (MSCs) are multipotent stromal cells that can differentiate into a variety of cell types despite their low numbers in heart tissue. Here, we sought to determine if SVF implantation into impaired heart tissue affected endogenous MSCs in the heart. Therefore, we investigated the expression levels of proteins associated with oxidation, inflammation, and apoptosis in MSCs co-cultured with adipose-derived adherent stromal cells (ADASs) from 6 donors' SVFs under oxidative stress conditions for their roles in many physiological processes in the heart. Interestingly, p53 pathway proteins and mitogen-activated protein kinase (MAPK) signalling pathway components were up-regulated by H 2 O 2 but exhibited a downward trend in MSCs co-cultured with ADASs. These data suggest that ADASs may inhibit oxidative stress-induced apoptosis in MSCs via the p53 and MAPK pathways. Our findings also suggest that the positive effects of SVF implantation into damaged heart tissue may be attributed to the various responses of MSCs. This finding may provide new insights for the clinical application of adipose-derived SVF transplantation in cardiac diseases. We investigated the expression levels of proteins associated with oxidation, inflammation, and apoptosis in MSCs co-cultured with isolated ADASs from 6 donors' SVFs under oxidative stress conditions. Our results imply that isolated ADASs from SVFs may inhibit oxidative stress-induced cell cycle arrest and/or apoptosis in MSCs via a p53-dependent pathway. Furthermore, we identified an anti-apoptotic mechanism involving oxidative stress-induced apoptosis by adipose-derived ADASs in MSCs for the first time. Our findings suggest that the positive effects of SVF implantation into damaged heart tissue may be attributed to the various actions of MSCs. © 2018 John Wiley & Sons, Ltd.

Targeting innate immunity for neurodegenerative disorders of the central nervous system.

PubMed

Andreasson, Katrin I; Bachstetter, Adam D; Colonna, Marco; Ginhoux, Florent; Holmes, Clive; Lamb, Bruce; Landreth, Gary; Lee, Daniel C; Low, Donovan; Lynch, Marina A; Monsonego, Alon; O'Banion, M Kerry; Pekny, Milos; Puschmann, Till; Russek-Blum, Niva; Sandusky, Leslie A; Selenica, Maj-Linda B; Takata, Kazuyuki; Teeling, Jessica; Town, Terrence; Van Eldik, Linda J

2016-09-01

Neuroinflammation is critically involved in numerous neurodegenerative diseases, and key signaling steps of innate immune activation hence represent promising therapeutic targets. This mini review series originated from the 4th Venusberg Meeting on Neuroinflammation held in Bonn, Germany, 7-9th May 2015, presenting updates on innate immunity in acute brain injury and chronic neurodegenerative disorders, such as traumatic brain injury and Alzheimer disease, on the role of astrocytes and microglia, as well as technical developments that may help elucidate neuroinflammatory mechanisms and establish clinical relevance. In this meeting report, a brief overview of physiological and pathological microglia morphology is followed by a synopsis on PGE2 receptors, insights into the role of arginine metabolism and further relevant aspects of neuroinflammation in various clinical settings, and concluded by a presentation of technical challenges and solutions when working with microglia and astrocyte cultures. Microglial ontogeny and induced pluripotent stem cell-derived microglia, advances of TREM2 signaling, and the cytokine paradox in Alzheimer's disease are further contributions to this article. Neuroinflammation is critically involved in numerous neurodegenerative diseases, and key signaling steps of innate immune activation hence represent promising therapeutic targets. This mini review series originated from the 4th Venusberg Meeting on Neuroinflammation held in Bonn, Germany, 7-9th May 2015, presenting updates on innate immunity in acute brain injury and chronic neurodegenerative disorders, such as traumatic brain injury and Alzheimer's disease, on the role of astrocytes and microglia, as well as technical developments that may help elucidate neuroinflammatory mechanisms and establish clinical relevance. In this meeting report, a brief overview on physiological and pathological microglia morphology is followed by a synopsis on PGE2 receptors, insights into the role of arginine metabolism and further relevant aspects of neuroinflammation in various clinical settings, and concluded by a presentation of technical challenges and solutions when working with microglia cultures. Microglial ontogeny and induced pluripotent stem cell-derived microglia, advances of TREM2 signaling, and the cytokine paradox in Alzheimer's disease are further contributions to this article. © 2016 International Society for Neurochemistry.

Cognitive insight in schizophrenia patients and their biological parents: a pilot study.

PubMed

Raffard, Stéphane; Bortolon, Catherine; Macgregor, Alexandra; Norton, Joanna; Boulenger, Jean-Philippe; El Haj, Mohamad; Capdevielle, Delphine

2014-11-01

Clinical insight in schizophrenia patients is partly associated with familial environment but has been poorly studied to date. We aimed to explore (1) the relationship between parents' cognitive insight and their offspring's; (2) the relationship between parents' cognitive insight and their clinical insight into the disease of their offspring; and (3) the clinical and cognitive determinants of cognitive insight in parents. Cognitive insight was assessed in 37 patient-biological parent pairs/dyads with the Beck Cognitive Insight Scale (BCIS). Other measures included the Scale to assess Unawareness of Mental Disorder and cognitive assessments. We found no significant association between parents' cognitive insight and their offspring's. Conversely, a positive association between parents' cognitive insight and parents' insight into their offspring's symptoms was found. Better awareness of their offspring's specific symptoms was associated with lower levels of overconfidence in one's beliefs and with BCIS total score. BCIS Self-Certainty and BCIS total score were associated with better executive functioning and verbal comprehension. Better insight into their offspring's symptoms is associated with cognitive insight in biological parents of schizophrenia patients. Our results support the integration of cognitive intervention targeting parents' cognitive flexibility in family psychoeducational programs and provide an important first step towards developing a more refined understanding of the factors involved in insight into symptoms of illness in parents of schizophrenia patients. Copyright © 2014 Elsevier B.V. All rights reserved.

Voxel-based magnetic resonance imaging investigation of poor and preserved clinical insight in people with schizophrenia

PubMed Central

Sapara, Adegboyega; Ffytche, Dominic H; Cooke, Michael A; Williams, Steven CR; Kumari, Veena

2016-01-01

AIM To define regional grey-matter abnormalities in schizophrenia patients with poor insight (Insight-), relative to patients with preserved clinical insight (Insight+), and healthy controls. METHODS Forty stable schizophrenia outpatients (20 Insight- and 20 Insight+) and 20 healthy controls underwent whole brain magnetic resonance imaging (MRI). Insight in all patients was assessed using the Birchwood Insight Scale (BIS; a self-report measure). The two patient groups were pre-selected to match on most clinical and demographic parameters but, by design, they had markedly distinct BIS scores. Voxel-based morphometry employed in SPM8 was used to examine group differences in grey matter volumes across the whole brain. RESULTS The three participant groups were comparable in age [F(2,57) = 0.34, P = 0.71] and the patient groups did not differ in age at illness onset [t(38) = 0.87, P = 0.39]. Insight- and Insight+ patient groups also did not differ in symptoms on the Positive and Negative Syndromes scale (PANSS): Positive symptoms [t(38) = 0.58, P = 0.57], negative symptoms [t(38) = 0.61, P = 0.55], general psychopathology [t(38) = 1.30, P = 0.20] and total PANSS scores [t(38) = 0.21, P = 0.84]. The two patient groups, as expected, varied significantly in the level of BIS-assessed insight [t(38) = 12.11, P < 0.001]. MRI results revealed lower fronto-temporal, parahippocampal, occipital and cerebellar grey matter volumes in Insight- patients, relative to Insight+ patients and healthy controls (for all clusters, family-wise error corrected P < 0.05). Insight+ patient and healthy controls did not differ significantly (P > 0.20) from each other. CONCLUSION Our findings demonstrate a clear association between poor clinical insight and smaller fronto-temporal, occipital and cerebellar grey matter volumes in stable long-term schizophrenia patients. PMID:27679770

A typology of uncertainty derived from an analysis of critical incidents in medical residents: A mixed methods study.

PubMed

Hamui-Sutton, Alicia; Vives-Varela, Tania; Gutiérrez-Barreto, Samuel; Leenen, Iwin; Sánchez-Mendiola, Melchor

2015-11-04

Medical uncertainty is inherently related to the practice of the physician and generally affects his or her patient care, job satisfaction, continuing education, as well as the overall goals of the health care system. In this paper, some new types of uncertainty, which extend existing typologies, are identified and the contexts and strategies to deal with them are studied. We carried out a mixed-methods study, consisting of a qualitative and a quantitative phase. For the qualitative study, 128 residents reported critical incidents in their clinical practice and described how they coped with the uncertainty in the situation. Each critical incident was analyzed and the most salient situations, 45 in total, were retained. In the quantitative phase, a distinct group of 120 medical residents indicated for each of these situations whether they have been involved in the described situations and, if so, which coping strategy they applied. The analysis examines the relation between characteristics of the situation and the coping strategies. From the qualitative study, a new typology of uncertainty was derived which distinguishes between technical, conceptual, communicational, systemic, and ethical uncertainty. The quantitative analysis showed that, independently of the type of uncertainty, critical incidents are most frequently resolved by consulting senior physicians (49 % overall), which underscores the importance of the hierarchical relationships in the hospital. The insights gained by this study are combined into an integrative model of uncertainty in medical residencies, which combines the type and perceived level of uncertainty, the strategies employed to deal with it, and context elements such as the actors present in the situation. The model considers the final resolution at each of three levels: the patient, the health system, and the physician's personal level. This study gives insight into how medical residents make decisions under different types of uncertainty, giving account of the context in which the interactions take place and of the strategies used to resolve the incidents. These insights may guide the development of organizational policies that reduce uncertainty and stress in residents during their clinical training.

Integrating research, clinical care, and education in academic health science centers.

PubMed

King, Gillian; Thomson, Nicole; Rothstein, Mitchell; Kingsnorth, Shauna; Parker, Kathryn

2016-10-10

Purpose One of the major issues faced by academic health science centers (AHSCs) is the need for mechanisms to foster the integration of research, clinical, and educational activities to achieve the vision of evidence-informed decision making (EIDM) and optimal client care. The paper aims to discuss this issue. Design/methodology/approach This paper synthesizes literature on organizational learning and collaboration, evidence-informed organizational decision making, and learning-based organizations to derive insights concerning the nature of effective workplace learning in AHSCs. Findings An evidence-informed model of collaborative workplace learning is proposed to aid the alignment of research, clinical, and educational functions in AHSCs. The model articulates relationships among AHSC academic functions and sub-functions, cross-functional activities, and collaborative learning processes, emphasizing the importance of cross-functional activities in enhancing collaborative learning processes and optimizing EIDM and client care. Cross-functional activities involving clinicians, researchers, and educators are hypothesized to be a primary vehicle for integration, supported by a learning-oriented workplace culture. These activities are distinct from interprofessional teams, which are clinical in nature. Four collaborative learning processes are specified that are enhanced in cross-functional activities or teamwork: co-constructing meaning, co-learning, co-producing knowledge, and co-using knowledge. Practical implications The model provides an aspirational vision and insight into the importance of cross-functional activities in enhancing workplace learning. The paper discusses the conceptual and empirical basis to the model, its contributions and limitations, and implications for AHSCs. Originality/value The model's potential utility for health care is discussed, with implications for organizational culture and the promotion of cross-functional activities.

Assessing stability in mild and moderate Parkinson's disease: Can clinical measures provide insight?

PubMed

Hubble, Ryan P; Silburn, Peter A; Naughton, Geraldine A; Cole, Michael H

2016-09-01

This cross-sectional study aimed to investigate the relationship between accelerometer-derived measures of movement rhythmicity and clinical measures of mobility, balance confidence and gait difficulty in people with Parkinson's disease (PD). Twenty-nine independently-living PD patients (Hoehn & Yahr Stages 1-3) with no history of significant injury or orthopaedic/deep brain stimulation surgery were recruited from a database of patients who had expressed an interest to participate in research. Participants completed clinical assessments of mobility, postural stability, balance confidence and symptom severity, while head and trunk rhythmicity was evaluated during gait using accelerometers. Following data collection, patients were stratified based on disease stage into either a Mild (Hoehn & Yahr Stage 1) or Moderate (Hoehn & Yahr Stages 2-3) PD group. The results highlighted that the Moderate PD group had poorer quality of life, reduced balance confidence and increased gait and falls difficulty. Furthermore, for these patients, gait disability and the number of previous falls were both negatively correlated with multiple components of head and trunk rhythmicity. For the Mild PD group, six-meter walk time was positively correlated with ML head rhythmicity and linear regression highlighted a significant predictive relationship between these outcomes. For the Mild and Moderate PD groups, balance confidence respectively predicted anterior-posterior trunk rhythmicity and vertical head rhythmicity. While these findings demonstrate that falls history and the Gait and Falls questionnaire provide moderate insight into head and trunk rhythmicity in Moderate PD patients, objective and clinically-feasible measures of postural instability would assist with the management of these symptoms. Copyright © 2016 Elsevier B.V. All rights reserved.

Circuit to Construct Mapping: A Mathematical Tool for Assisting the Diagnosis and Treatment in Major Depressive Disorder

PubMed Central

Bielczyk, Natalia Z.; Buitelaar, Jan K.; Glennon, Jeffrey C.; Tiesinga, Paul H. E.

2015-01-01

Major depressive disorder (MDD) is a serious condition with a lifetime prevalence exceeding 16% worldwide. MDD is a heterogeneous disorder that involves multiple behavioral symptoms on the one hand and multiple neuronal circuits on the other hand. In this review, we integrate the literature on cognitive and physiological biomarkers of MDD with the insights derived from mathematical models of brain networks, especially models that can be used for fMRI datasets. We refer to the recent NIH research domain criteria initiative, in which a concept of “constructs” as functional units of mental disorders is introduced. Constructs are biomarkers present at multiple levels of brain functioning – cognition, genetics, brain anatomy, and neurophysiology. In this review, we propose a new approach which we called circuit to construct mapping (CCM), which aims to characterize causal relations between the underlying network dynamics (as the cause) and the constructs referring to the clinical symptoms of MDD (as the effect). CCM involves extracting diagnostic categories from behavioral data, linking circuits that are causal to these categories with use of clinical neuroimaging data, and modeling the dynamics of the emerging circuits with attractor dynamics in order to provide new, neuroimaging-related biomarkers for MDD. The CCM approach optimizes the clinical diagnosis and patient stratification. It also addresses the recent demand for linking circuits to behavior, and provides a new insight into clinical treatment by investigating the dynamics of neuronal circuits underneath cognitive dimensions of MDD. CCM can serve as a new regime toward personalized medicine, assisting the diagnosis and treatment of MDD. PMID:25767450

In Vitro Expression of Cytokeratin 19 in Adipose-Derived Stem Cells Is Induced by Epidermal Growth Factor.

PubMed

Chen, Shangliang; Wang, Mingzhu; Chen, Xinglu; Chen, Shaolian; Liu, Li; Zhu, Jianbin; Wang, Jinhui; Yang, Xiaorong; Cai, Xiangsheng

2018-06-21

BACKGROUND Cytokeratin 19 (CK19) is a typical epithelial marker. In this study, we determined whether epidermal growth factor (EGF) or basic fibroblast growth factor (bFGF) could enhance CK19 expression in adipose-derived stem cells (ADSCs), thereby inducing the differentiation of ADSCs into epithelial-like cells. MATERIAL AND METHODS ADSCs were isolated from perinephric fat, and the expression of CD29, CD90, and CD105 was confirmed. Following isolation, ADSCs were cultured in static medium or medium containing EGF or bFGF. RESULTS Flow cytometry revealed that EGF and bFGF could alter mesenchymal stem cell markers as well as the cell cycle of ADSCs. Western blotting and immunofluorescence revealed that after 14 days, EGF treatment enhanced the expression of CK19 in ADSCs. CONCLUSIONS Our findings offer important insight for the clinical use of ADSCs in the generation of epithelial-like cells in the future.

First Insights into Human Fingertip Regeneration by Echo-Doppler Imaging and Wound Microenvironment Assessment.

PubMed

Jafari, Paris; Muller, Camillo; Grognuz, Anthony; Applegate, Lee Ann; Raffoul, Wassim; di Summa, Pietro G; Durand, Sébastien

2017-05-13

Fingertip response to trauma represents a fascinating example of tissue regeneration. Regeneration derives from proliferative mesenchymal cells (blastema) that subsequently differentiate into soft and skeletal tissues. Clinically, conservative treatment of the amputated fingertip under occlusive dressing can shift the response to tissue loss from a wound repair process towards regeneration. When analyzing by Immunoassay the wound exudate from occlusive dressings, the concentrations of brain-derived neurotrophic factor (BDNF) and leukemia inhibitory factor (LIF) were higher in fingertip exudates than in burn wounds (used as controls for wound repair versus regeneration). Vascular endothelial growth factor A (VEGF-A) and platelet-derived growth factor (PDGF) were highly expressed in both samples in comparable levels. In our study, pro-inflammatory cytokines were relatively higher expressed in regenerative fingertips than in the burn wound exudates while chemokines were present in lower levels. Functional, vascular and mechanical properties of the regenerated fingertips were analyzed three months after trauma and the data were compared to the corresponding fingertip on the collateral uninjured side. While sensory recovery and morphology (pulp thickness and texture) were similar to uninjured sides, mechanical parameters (elasticity, vascularization) were increased in the regenerated fingertips. Further studies should be done to clarify the importance of inflammatory cells, immunity and growth factors in determining the outcome of the regenerative process and its influence on the clinical outcome.

First Insights into Human Fingertip Regeneration by Echo-Doppler Imaging and Wound Microenvironment Assessment

PubMed Central

Jafari, Paris; Muller, Camillo; Grognuz, Anthony; Applegate, Lee Ann; Raffoul, Wassim; di Summa, Pietro G.; Durand, Sébastien

2017-01-01

Fingertip response to trauma represents a fascinating example of tissue regeneration. Regeneration derives from proliferative mesenchymal cells (blastema) that subsequently differentiate into soft and skeletal tissues. Clinically, conservative treatment of the amputated fingertip under occlusive dressing can shift the response to tissue loss from a wound repair process towards regeneration. When analyzing by Immunoassay the wound exudate from occlusive dressings, the concentrations of brain-derived neurotrophic factor (BDNF) and leukemia inhibitory factor (LIF) were higher in fingertip exudates than in burn wounds (used as controls for wound repair versus regeneration). Vascular endothelial growth factor A (VEGF-A) and platelet-derived growth factor (PDGF) were highly expressed in both samples in comparable levels. In our study, pro-inflammatory cytokines were relatively higher expressed in regenerative fingertips than in the burn wound exudates while chemokines were present in lower levels. Functional, vascular and mechanical properties of the regenerated fingertips were analyzed three months after trauma and the data were compared to the corresponding fingertip on the collateral uninjured side. While sensory recovery and morphology (pulp thickness and texture) were similar to uninjured sides, mechanical parameters (elasticity, vascularization) were increased in the regenerated fingertips. Further studies should be done to clarify the importance of inflammatory cells, immunity and growth factors in determining the outcome of the regenerative process and its influence on the clinical outcome. PMID:28505080

Vascular tissue engineering: towards the next generation vascular grafts.

PubMed

Naito, Yuji; Shinoka, Toshiharu; Duncan, Daniel; Hibino, Narutoshi; Solomon, Daniel; Cleary, Muriel; Rathore, Animesh; Fein, Corey; Church, Spencer; Breuer, Christopher

2011-04-30

The application of tissue engineering technology to cardiovascular surgery holds great promise for improving outcomes in patients with cardiovascular diseases. Currently used synthetic vascular grafts have several limitations including thrombogenicity, increased risk of infection, and lack of growth potential. We have completed the first clinical trial evaluating the feasibility of using tissue engineered vascular grafts (TEVG) created by seeding autologous bone marrow-derived mononuclear cells (BM-MNC) onto biodegradable tubular scaffolds. Despite an excellent safety profile, data from the clinical trial suggest that the primary graft related complication of the TEVG is stenosis, affecting approximately 16% of grafts within the first seven years after implantation. Continued investigation into the cellular and molecular mechanisms underlying vascular neotissue formation will improve our basic understanding and provide insights that will enable the rationale design of second generation TEVG. Published by Elsevier B.V.

Pathogenic mechanisms and therapeutic strategies in spinobulbar muscular atrophy

PubMed Central

Chua, Jason P.; Lieberman, Andrew P.

2014-01-01

We review the genetic and clinical features of spinobulbar muscular atrophy (SBMA), a progressive neuromuscular disorder caused by a CAG/glutamine tract expansion in the androgen receptor. SBMA was the first polyglutamine disease to be discovered, and we compare and contrast it with related degenerative disorders of the nervous system caused by expanded glutamine tracts. We review the cellular and animals models that have been most widely used to study this disorder, and highlight insights into disease pathogenesis derived from this work. These model systems have revealed critical aspects of the disease, including its hormone dependence, a feature that underlies disease occurrence only in men with the mutant allele. We discuss how this and other findings have been translated to clinical trials for SBMA patients, and examine emerging therapeutic targets that have been identified by recent work. PMID:24040817

Current Status and Future Prospects of Marine Natural Products (MNPs) as Antimicrobials.

PubMed

Choudhary, Alka; Naughton, Lynn M; Montánchez, Itxaso; Dobson, Alan D W; Rai, Dilip K

2017-08-28

The marine environment is a rich source of chemically diverse, biologically active natural products, and serves as an invaluable resource in the ongoing search for novel antimicrobial compounds. Recent advances in extraction and isolation techniques, and in state-of-the-art technologies involved in organic synthesis and chemical structure elucidation, have accelerated the numbers of antimicrobial molecules originating from the ocean moving into clinical trials. The chemical diversity associated with these marine-derived molecules is immense, varying from simple linear peptides and fatty acids to complex alkaloids, terpenes and polyketides, etc. Such an array of structurally distinct molecules performs functionally diverse biological activities against many pathogenic bacteria and fungi, making marine-derived natural products valuable commodities, particularly in the current age of antimicrobial resistance. In this review, we have highlighted several marine-derived natural products (and their synthetic derivatives), which have gained recognition as effective antimicrobial agents over the past five years (2012-2017). These natural products have been categorized based on their chemical structures and the structure-activity mediated relationships of some of these bioactive molecules have been discussed. Finally, we have provided an insight into how genome mining efforts are likely to expedite the discovery of novel antimicrobial compounds.

Transgene Reactivation in Induced Pluripotent Stem Cell Derivatives and Reversion to Pluripotency of Induced Pluripotent Stem Cell-Derived Mesenchymal Stem Cells

PubMed Central

Galat, Yekaterina; Perepitchka, Mariana; Jennings, Lawrence J.; Iannaccone, Philip M.; Hendrix, Mary J.C.

2016-01-01

Induced pluripotent stem cells (iPSCs) have enormous potential in regenerative medicine and disease modeling. It is now felt that clinical trials should be performed with iPSCs derived with nonintegrative constructs. Numerous studies, however, including those describing disease models, are still being published using cells derived from iPSCs generated with integrative constructs. Our experimental work presents the first evidence of spontaneous transgene reactivation in vitro in several cellular types. Our results show that the transgenes were predominantly silent in parent iPSCs, but in mesenchymal and endothelial iPSC derivatives, the transgenes experienced random upregulation of Nanog and c-Myc. Additionally, we provide evidence of spontaneous secondary reprogramming and reversion to pluripotency in mesenchymal stem cells derived from iPSCs. These findings strongly suggest that the studies, which use cellular products derived from iPSCs generated with retro- or lentiviruses, should be evaluated with consideration of the possibility of transgene reactivation. The in vitro model described here provides insight into the earliest events of culture transformation and suggests the hypothesis that reversion to pluripotency may be responsible for the development of tumors in cell replacement experiments. The main goal of this work, however, is to communicate the possibility of transgene reactivation in retro- or lenti-iPSC derivatives and the associated loss of cellular fidelity in vitro, which may impact the outcomes of disease modeling and related experimentation. PMID:27193052

Microbiome Composition and Function Drives Wound-Healing Impairment in the Female Genital Tract

PubMed Central

Arnold, Kelly; Romas, Laura; Westmacott, Garrett; McCorrister, Stuart; McKinnon, Lyle R.; Cohen, Craig R.; Mackelprang, Romel; Lingappa, Jairam; Lauffenburger, Doug A.; Klatt, Nichole R.; Burgener, Adam D.

2016-01-01

The mechanism(s) by which bacterial communities impact susceptibility to infectious diseases, such as HIV, and maintain female genital tract (FGT) health are poorly understood. Evaluation of FGT bacteria has predominantly been limited to studies of species abundance, but not bacterial function. We therefore sought to examine the relationship of bacterial community composition and function with mucosal epithelial barrier health in the context of bacterial vaginosis (BV) using metaproteomic, metagenomic, and in vitro approaches. We found highly diverse bacterial communities dominated by Gardnerella vaginalis associated with host epithelial barrier disruption and enhanced immune activation, and low diversity communities dominated by Lactobacillus species that associated with lower Nugent scores, reduced pH, and expression of host mucosal proteins important for maintaining epithelial integrity. Importantly, proteomic signatures of disrupted epithelial integrity associated with G. vaginalis-dominated communities in the absence of clinical BV diagnosis. Because traditional clinical assessments did not capture this, it likely represents a larger underrepresented phenomenon in populations with high prevalence of G. vaginalis. We finally demonstrated that soluble products derived from G. vaginalis inhibited wound healing, while those derived from L. iners did not, providing insight into functional mechanisms by which FGT bacterial communities affect epithelial barrier integrity. PMID:27656899

Fractal mechanisms in the electrophysiology of the heart

NASA Technical Reports Server (NTRS)

Goldberger, A. L.

1992-01-01

The mathematical concept of fractals provides insights into complex anatomic branching structures that lack a characteristic (single) length scale, and certain complex physiologic processes, such as heart rate regulation, that lack a single time scale. Heart rate control is perturbed by alterations in neuro-autonomic function in a number of important clinical syndromes, including sudden cardiac death, congestive failure, cocaine intoxication, fetal distress, space sickness and physiologic aging. These conditions are associated with a loss of the normal fractal complexity of interbeat interval dynamics. Such changes, which may not be detectable using conventional statistics, can be quantified using new methods derived from "chaos theory.".

Strain-specific estimation of epidemic success provides insights into the transmission dynamics of tuberculosis

PubMed Central

Rasigade, Jean-Philippe; Barbier, Maxime; Dumitrescu, Oana; Pichat, Catherine; Carret, Gérard; Ronnaux-Baron, Anne-Sophie; Blasquez, Ghislaine; Godin-Benhaim, Christine; Boisset, Sandrine; Carricajo, Anne; Jacomo, Véronique; Fredenucci, Isabelle; Pérouse de Montclos, Michèle; Flandrois, Jean-Pierre; Ader, Florence; Supply, Philip; Lina, Gérard; Wirth, Thierry

2017-01-01

The transmission dynamics of tuberculosis involves complex interactions of socio-economic and, possibly, microbiological factors. We describe an analytical framework to infer factors of epidemic success based on the joint analysis of epidemiological, clinical and pathogen genetic data. We derive isolate-specific, genetic distance-based estimates of epidemic success, and we represent success-related time-dependent concepts, namely epidemicity and endemicity, by restricting analysis to specific time scales. The method is applied to analyze a surveillance-based cohort of 1,641 tuberculosis patients with minisatellite-based isolate genotypes. Known predictors of isolate endemicity (older age, native status) and epidemicity (younger age, sputum smear positivity) were identified with high confidence (P < 0.001). Long-term epidemic success also correlated with the ability of Euro-American and Beijing MTBC lineages to cause active pulmonary infection, independent of patient age and country of origin. Our results demonstrate how important insights into the transmission dynamics of tuberculosis can be gained from active surveillance data. PMID:28349973

Curcumin therapeutic promises and bioavailability in colorectal cancer.

PubMed

Shehzad, A; Khan, S; Shehzad, O; Lee, Y S

2010-07-01

Curcumin, a polyphenol and derivative of turmeric is one of the most commonly used and highly researched phytochemicals. Several research studies have provided interesting insights into the multiple mechanisms by which curcumin may mediate chemotherapy and chemopreventive effects on cancers, including colorectal cancer. Curcumin has the ability to inhibit carcinogenic promotion of colorectal cancer through the modulation of multiple molecular targets such as transcription factors, enzymes, cell cycle proteins, cell surface adhesion proteins, survival pathways and cytokines. A number of clinical trials dealing with curcumin's efficacy and safety revealed poor absorption and low bioavailability. Different factors contributing to the low bioavailability include low plasma level, tissue distribution, rapid metabolism and elimination from the body. Although, curcumin poor absorption and low systemic bioavailability limit its translation into clinics, some of the methods for its use can be approached to enhance the absorption and achieve a therapeutic level of curcumin. Recent clinical trials suggest a potential role for curcumin in regards to colorectal cancer therapy.

Distinct Roles of Cervical Epithelia and Stroma in Pregnancy and Parturition.

PubMed

Nallasamy, Shanmugasundaram; Mahendroo, Mala

2017-03-01

Through pregnancy the cervix must simultaneously remain competent for pregnancy maintenance and yet become progressively compliant to ensure on time parturition. Cervical changes precede not only term but also preterm birth. Thus, an understanding of the molecular mechanisms by which the cervix maintains the delicate balance between competence and compliance is required to prevent the potential for lifelong health complications that can result from a premature birth. Recent advances and accumulating evidence support distinct roles for the cervical epithelia and stroma in sustaining competence. Concurrently, structural reorganization of the stromal extracellular matrix allows for the gradual decline in tissue compliance. In recent years, advances in our understanding of the cervical remodeling process has resulted from the collective insights derived from biological, genomics, engineering, and mathematical modeling studies on clinical samples and animal models. This review will highlight recent literature that advances understanding of (1) the importance of barrier function in the lower female reproductive tract in protection against ascending infection, (2) cellular and extracellular matrix changes in the cervical stroma that influence the mechanical function of the cervix, (3) the potential translation of biological insights into clinical tools that impact preterm birth, and (4) the distinction between term and specific pathways of preterm birth. Finally, we present a discussion of future areas of investigation that are likely to advance understanding and lead to the development of clinical tools for accurate detection and prevention of premature birth. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

The Association of Insight and Change in Insight with Clinical Symptoms in Depressed Inpatients.

PubMed

He, Hongbo; Chang, Qing; Ma, Yarong

2018-04-25

Lack of insight has been extensively studied and was found to be adversely correlated with impaired treatment compliance and worse long term clinical outcomes among patients with schizophrenia, while not much is known about this phenonmenon in patients with severe depression. To explore the correlates of insight and its relation to symptom changes among the most seriously ill patients with affective disorders, those who require hospitalization. Patients hospitalized in a large psychiatric hospital in south China with either major depressive disorder (MDD)(N=55) or bipolar depression (BD) (N=85) based on ICD-10 diagnostic criteria were assessed with the Insight and Treatment Attitudes Questionnaire (ITAQ) one week after admission and at the time of discharge. Clinical symptoms were measured at the same time with the Hamilton Rating Scale for Depression (HAMD-17) and the Depression subscale of the Symptom Check list-90 (SCL-90). Length of stay (LOS), duration of illness, duration of untreated mood disorder, number of previous episodes of depression and previous admissions for depression were documented during interviews with patients and their families and from a review of medical records. Bivariate correlations and multiple regression analysis were used to examine the relationship of sociodemographic characteristics, clinical symptomatology and clinical history, to insight at the time of admission. The relationships between change in clinical symptoms and change in insight from admission to discharge were also examined. Stepwise multiple regression models suggested that any previous admissions for depression and higher anxiety factor scores on the HAMD-17 are significant independent predictors of insight accounting for 22.9% of the variance. Multiple regression analysis residual change scores (change scores adjusted for baseline values) on the ITAQ showed that improved insight over average stays of 51 days were inversely related to the residual psychomotor retardation factor on the HAMD-17 accounting for 9.1% of the variance. More severe anxiety symptoms and previous hospitalization for depression were associated with greater insight into illness at admission. Reduction of motor retardation symptoms during treatment was associated with greater improvement in insight to the time of discharge. The patients who are sicker at admission and who show more improvement in psychomotor retardation show the greatest insight.

The Association of Insight and Change in Insight with Clinical Symptoms in Depressed Inpatients

PubMed Central

HE, Hongbo; CHANG, Qing; MA, Yarong

2018-01-01

Background Lack of insight has been extensively studied and was found to be adversely correlated with impaired treatment compliance and worse long term clinical outcomes among patients with schizophrenia, while not much is known about this phenonmenon in patients with severe depression. Aim To explore the correlates of insight and its relation to symptom changes among the most seriously ill patients with affective disorders, those who require hospitalization. Methods Patients hospitalized in a large psychiatric hospital in south China with either major depressive disorder (MDD)(N=55) or bipolar depression (BD) (N=85) based on ICD-10 diagnostic criteria were assessed with the Insight and Treatment Attitudes Questionnaire (ITAQ) one week after admission and at the time of discharge. Clinical symptoms were measured at the same time with the Hamilton Rating Scale for Depression (HAMD-17) and the Depression subscale of the Symptom Check list-90 (SCL-90). Length of stay (LOS), duration of illness, duration of untreated mood disorder, number of previous episodes of depression and previous admissions for depression were documented during interviews with patients and their families and from a review of medical records. Bivariate correlations and multiple regression analysis were used to examine the relationship of sociodemographic characteristics, clinical symptomatology and clinical history, to insight at the time of admission. The relationships between change in clinical symptoms and change in insight from admission to discharge were also examined. Results Stepwise multiple regression models suggested that any previous admissions for depression and higher anxiety factor scores on the HAMD-17 are significant independent predictors of insight accounting for 22.9% of the variance. Multiple regression analysis residual change scores (change scores adjusted for baseline values) on the ITAQ showed that improved insight over average stays of 51 days were inversely related to the residual psychomotor retardation factor on the HAMD-17 accounting for 9.1% of the variance. Conclusions More severe anxiety symptoms and previous hospitalization for depression were associated with greater insight into illness at admission. Reduction of motor retardation symptoms during treatment was associated with greater improvement in insight to the time of discharge. The patients who are sicker at admission and who show more improvement in psychomotor retardation show the greatest insight. PMID:29736131

Clinical and neuropsychological correlates of insight in schizophrenia and bipolar I disorder: does diagnosis matter?

PubMed

Varga, Monica; Magnusson, Andres; Flekkøy, Kjell; David, Anthony S; Opjordsmoen, Stein

2007-01-01

Lack of insight is a well-recognized feature of schizophrenia and is associated with symptom severity and cognitive impairments. However, the diagnostic specificity of insight variables and their correlates is not known. To assess this specificity, we compared awareness of illness and neuropsychological function between patients with chronic schizophrenia and bipolar I disorder. We assessed insight, level of psychopathology, and cognitive performance on a neuropsychological test battery in 37 patients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition bipolar I disorder, 32 patients with schizophrenia, and 31 healthy subjects for comparison. There was no significant difference between the 2 diagnostic groups on general illness awareness. However, patients with bipolar disorder had better awareness of their symptoms and their pathologic nature compared to patients with schizophrenia. Similar patterns of association emerged between insight and clinical variables. General unawareness was associated with clinical severity, especially of the affective type, and working memory deficits (Wechsler Adult Intelligence Scale digit span) in both diagnostic groups. The contribution of other cognitive deficits to insight differed across the groups. Misattribution differed from the other aspects of insight in its relative independence of clinical and neurocognitive correlates. Both patient groups were neurocognitively impaired, with the schizophrenia group performing significantly worse on conceptual ability, verbal learning, visuospatial processing, and motor speed. The results suggest that differences in general insight in major mental disorders may be explained by symptom severity and working memory function rather than the specific diagnosis. Subcomponents of insight are influenced by different factors emphasizing the need to consider insight as multidimensional.

Is it me? Verbal self-monitoring neural network and clinical insight in schizophrenia

PubMed Central

Sapara, Adegboyega; ffytche, Dominic H.; Cooke, Michael A.; Williams, Steven C.R.; Kumari, Veena

2015-01-01

Self-monitoring, defined as the ability to distinguish between self-generated stimuli from other-generated ones, is known to be impaired in schizophrenia. This impairment has been theorised as the basis for many of the core psychotic symptoms, in particular, poor clinical insight. This study aimed to investigate verbal self-monitoring related neural substrates of preserved and poor clinical insight in schizophrenia. It involved 40 stable schizophrenia outpatients, 20 with preserved and 20 with poor insight, and 20 healthy participants. All participants underwent functional magnetic resonance imaging with brain coverage covering key areas in the self-monitoring network during a verbal self-monitoring task. Healthy participants showed higher performance accuracy and greater thalamic activity than both preserved and poor insight patient groups. Preserved insight patients showed higher activity in the putamen extending into the caudate, insula and inferior frontal gyrus, compared to poor insight patients, and in the anterior cingulate and medial frontal gyrus, compared to healthy participants. Poor insight patients did not show greater activity in any brain area compared to preserved insight patients or healthy participants. Future studies may pursue therapeutic avenues, such as meta-cognitive therapies to promote self-monitoring or targeted stimulation of relevant brain areas, as means of enhancing insight in schizophrenia. PMID:26549744

Searching for Clinically Relevant Biomarkers in Geriatric Oncology.

PubMed

Katsila, Theodora; Patrinos, George P; Kardamakis, Dimitrios

2018-01-01

Ageing, which is associated with a progressive decline and functional deterioration in multiple organ systems, is highly heterogeneous, both inter- and intraindividually. For this, tailored-made theranostics and optimum patient stratification become fundamental, when decision-making in elderly patients is considered. In particular, when cancer incidence and cancer-related mortality and morbidity are taken into account, elderly patient care is a public health concern. In this review, we focus on oncogeriatrics and highlight current opportunities and challenges with an emphasis on the unmet need of clinically relevant biomarkers in elderly cancer patients. We performed a literature search on PubMed and Scopus databases for articles published in English between 2000 and 2017 coupled to text mining and analysis. Considering the top insights, we derived from our literature analysis that information knowledge needs to turn into knowledge growth in oncogeriatrics towards clinically relevant biomarkers, cost-effective practices, updated educational schemes for health professionals (in particular, geriatricians and oncologists), and awareness of ethical issues. We conclude with an interdisciplinary call to omics, geriatricians, oncologists, informatics, and policy-makers communities that Big Data should be translated into decision-making in the clinic.

The relationship between clinical insight and cognitive and affective empathy in schizophrenia.

PubMed

Atoui, Mia; El Jamil, Fatima; El Khoury, Joseph; Doumit, Mark; Syriani, Nathalie; Khani, Munir; Nahas, Ziad

2018-06-01

Schizophrenia is often associated with poor clinical insight (unawareness of mental illness and its symptoms) and deficits in empathy, which are important for social functioning. Cognitive empathy has been linked to clinical insight while affective empathy and its role in insight and pathology have received mixed evidence. Instruments assessing symptomatology (Positive and Negative Syndrome Scale; PANSS), clinical insight (Scales to assess awareness of mental disorders; SUMD), and cognitive and affective empathy were administered to 22 participants with first episode and chronic schizophrenia and 21 healthy controls. Self-report, parent-report, and performance based measures were used to assess cognitive and affective empathy (The interpersonal reactivity index; IRI/Reading the Mind in the Eyes Test/Faux Pas) to reduce bias and parse shared variance. Age of onset, gender, and symptomatology emerged as significant predictors of poor clinical insight. Additionally, the fantasy subscale of the IRI as reported by parents emerged as a positive predictor while the personal distress (parent report) subscale emerged as a negative predictor of awareness into mental illness. There were significant differences on performance-based measures of empathy between the control and schizophrenia groups. Findings suggest that affective empathy is relatively intact across phases of illness whereas cognitive empathy abilities are compromised and could be targets for psychotherapy intervention.

T Cells Redirected to a Minor Histocompatibility Antigen Instruct Intratumoral TNFα Expression and Empower Adoptive Cell Therapy for Solid Tumors.

PubMed

Manzo, Teresa; Sturmheit, Tabea; Basso, Veronica; Petrozziello, Elisabetta; Hess Michelini, Rodrigo; Riba, Michela; Freschi, Massimo; Elia, Angela R; Grioni, Matteo; Curnis, Flavio; Protti, Maria Pia; Schumacher, Ton N; Debets, Reno; Swartz, Melody A; Corti, Angelo; Bellone, Matteo; Mondino, Anna

2017-02-01

Donor-derived allogeneic T cells evoke potent graft versus tumor (GVT) effects likely due to the simultaneous recognition of tumor-specific and host-restricted minor histocompatibility (H) antigens. Here we investigated whether such effects could be reproduced in autologous settings by TCR gene-engineered lymphocytes. We report that T cells redirected either to a broadly expressed Y-encoded minor H antigen or to a tumor-associated antigen, although poorly effective if individually transferred, when simultaneously administered enabled acute autochthonous tumor debulking and resulted in durable clinical remission. Y-redirected T cells proved hyporesponsive in peripheral lymphoid organs, whereas they retained effector function at the tumor site, where in synergy with tumor-redirected lymphocytes, they instructed TNFα expression, endothelial cell activation, and intratumoral T-cell infiltration. While neutralizing TNFα hindered GVT effects by the combined T-cell infusion, a single injection of picogram amounts of NGR-TNF, a tumor vessel-targeted TNFα derivative currently in phase III clinical trials, substituted for Y-redirected cells and enabled tumor debulking by tumor-redirected lymphocytes. Together, our results provide new mechanistic insights into allogeneic GVT, validate the importance of targeting the tumor and its associated stroma, and prove the potency of a novel combined approach suitable for immediate clinical implementation. Cancer Res; 77(3); 658-71. ©2016 AACR. ©2016 American Association for Cancer Research.

Variability in Platelet-Derived Growth Factor Receptor Alpha Antibody Specificity May Impact Clinical Utility of Immunohistochemistry Assays

PubMed Central

Holzer, Timothy R.; O’Neill Reising, Leslie; Credille, Kelly M.; Schade, Andrew E.; Oakley, Gerard J.

2016-01-01

Aberrant regulation of the receptor tyrosine kinase platelet-derived growth factor alpha (PDGFRα) is implicated in several types of cancer. Inhibition of the PDGFRα pathway may be a beneficial therapy, and detection of PDGFRα in tumor biopsies may lead to insights about which patients respond to therapy. Exploratory or clinical biomarker use of PDGFRα IHC has been frequently reported, often with polyclonal antibody sc-338. An sc-338-based assay was systematically compared with anti-PDGFRα rabbit monoclonal antibody D13C6 using immunoblot profiling and IHC in formalin-fixed and paraffin-embedded human tumor cell lines. Application of sc-338 to blots of whole cell lysates showed multiple bands including some of unknown origin, whereas application of D13C6 resulted in a prominent band at the expected molecular mass of PDGFRα. The IHC assay using D13C6 showed appropriate staining in cell lines, whereas the assay using sc-338 suggested nonspecific detection of proteins. An optimized IHC assay using D13C6 showed a range of staining in the tumor stromal compartment in lung and ovarian carcinomas. These observations suggest that use of clone sc-338 produced unreliable results and should not be used for an IHC research grade assay. In addition, this precludes its use as a potential antibody for a clinical diagnostic tool. PMID:27837159

Insight into mental illness and child maltreatment risk among mothers with major psychiatric disorders.

PubMed

Mullick, M; Miller, L J; Jacobsen, T

2001-04-01

This study examined the relationship between insight into mental illness and current child maltreatment risk among mothers who had a major psychiatric disorder and who had lost custody of a child because of abuse, neglect, or having placed the child at risk of harm. Specifically, a measure of insight was examined in relation to systematically observed parenting behaviors known to be correlated with past child maltreatment and in relation to a comprehensive clinical determination of risk. Forty-four mothers who had a major psychiatric disorder were independently rated for their insight into their illness, the quality of mother-child interaction, and the overall clinical risk of maltreatment. Better insight into mental illness was associated with more sensitive mothering behavior and with lower assessed clinical risk of maltreatment. The association remained when mothers with current psychotic symptoms were excluded from the analyses. Better insight did not appear to be associated with past psychotic symptoms, maternal psychiatric diagnosis, or the mother's level of education. Insight into mental illness may function as a protective factor that influences the risk of child maltreatment in mothers with mental illness. Measures of insight could be usefully incorporated into comprehensive parenting assessments for mothers with psychiatric disorders.

New Insights into the Role of the Immune Microenvironment in Breast Carcinoma

PubMed Central

de la Cruz-Merino, Luis; Barco-Sánchez, Antonio; Henao Carrasco, Fernando; Nogales Fernández, Esteban; Vallejo Benítez, Ana; Brugal Molina, Javier; Martínez Peinado, Antonio; Grueso López, Ana; Ruiz Borrego, Manuel; Codes Manuel de Villena, Manuel; Sánchez-Margalet, Víctor; Nieto-García, Adoración; Alba Conejo, Emilio; Casares Lagar, Noelia; Ibáñez Martínez, José

2013-01-01

Recently, immune edition has been recognized as a new hallmark of cancer. In this respect, some clinical trials in breast cancer have reported imppressive outcomes related to laboratory immune findings, especially in the neoadjuvant and metastatic setting. Infiltration by tumor infiltrating lymphocytes (TIL) and their subtypes, tumor-associated macrophages (TAM) and myeloid-derived suppressive cells (MDSC) seem bona fide prognostic and even predictive biomarkers, that will eventually be incorporated into diagnostic and therapeutic algorithms of breast cancer. In addition, the complex interaction of costimulatory and coinhibitory molecules on the immune synapse and the different signals that they may exert represent another exciting field to explore. In this review we try to summarize and elucidate these new concepts and knowledge from a translational perspective focusing on breast cancer, paying special attention to those aspects that might have more significance in clinical practice and could be useful to design successful therapeutic strategies in the future. PMID:23861693

Psychosis: clinical insight and beliefs in immigrants in their first episode.

PubMed

Berg, Akiah Ottesen; Barrett, Elizabeth Ann; Nerhus, Mari; Büchman, Camilla; Simonsen, Carmen; Faerden, Ann; Andreassen, Ole A; Melle, Ingrid

2018-04-01

Lack of insight into illness is frequent in psychotic disorders and seen as part of their primary pathology. The recognition of symptoms as psychotic, and beliefs about treatment alternatives, is also influenced by socio-cultural factors. Here we examined clinical insight into illness and beliefs about psychosis in immigrants in their first episode of psychosis compared with a reference group. A total of 277 first-episode psychosis participants were recruited to this cross-sectional study; 40 first- and 40 second-generation immigrants from Europe, Americas and Oceania (n = 37), Asia including Turkey (n = 28) or Africa (n = 15). The Birchwood Insight Scale was used to measure clinical insight and 'The Attitudes and Beliefs about Mental Health Problems' schizophrenia version to assess socio-cultural beliefs. Immigrants did not differ from the reference sample in clinical insight. After controlling for education level, first-generation immigrants were less likely to recognize psychotic symptoms (odds ratio (OR) 2.9; Wald = 8.977, degrees of freedom (d.f.) 1, P = 0.003) and viewed hospitalization (OR 5.2; Wald = 20.388, d.f. 1, P = 0.001) and treatment by a psychiatrist (OR 4.9; Wald = 6.609, d.f. 1, P = 0.01)) as less beneficial than the reference group. Immigrants from Asia held more alternative explanations (OR 0.3; Wald = 6.567, d.f. 1, P = 0.010). There were significantly stronger associations between clinical insight and socio-cultural beliefs in the reference group. Socio-cultural beliefs about psychosis in immigrants in first-episode psychosis call for more tailored information to this group, and emphasize the importance of treatment interventions involving both a cultural and personal perspective of insight. © 2015 Wiley Publishing Asia Pty Ltd.

The relationship between cognitive insight and depression in psychosis and schizophrenia: a review and meta-analysis.

PubMed

Palmer, Emma C; Gilleen, James; David, Anthony S

2015-08-01

Lack of insight is a commonly observed problem in patients with psychosis and schizophrenia. Clinical insight in patients has been associated with low mood. Cognitive insight is a recently defined concept, relating to the ability to self-reflect and the degree to which patients are over-confident regarding their interpretations of illness-related experiences, and is related to clinical insight. We therefore sought to investigate whether there is a positive relationship between cognitive insight and mood. A literature search identified 17 relevant papers published between 2004 and 2014. Our analysis indicated that there was a small but significant positive correlation between the composite index (CI) of the Beck Cognitive Insight Scale (BCIS) and depression scores, but this was driven by a significant positive relationship between depression and the BCIS self-reflection (SR) sub-scale, where low mood was related to higher SR scores. There was no significant relationship between the self-certainty sub-scale and depression. Post-hoc analysis indicated that different depression scales did not significantly affect the relationship with SR. Our results support the idea that cognitive insight is significantly related to mood in schizophrenia, and the effect size is similar to that between clinical insight and mood. Potential applications of this knowledge into treatment and rehabilitation are discussed and a model of cognitive insight is proposed. Copyright © 2015 Elsevier B.V. All rights reserved.

Is it me? Verbal self-monitoring neural network and clinical insight in schizophrenia.

PubMed

Sapara, Adegboyega; Ffytche, Dominic H; Cooke, Michael A; Williams, Steven C R; Kumari, Veena

2015-12-30

Self-monitoring, defined as the ability to distinguish between self-generated stimuli from other-generated ones, is known to be impaired in schizophrenia. This impairment has been theorised as the basis for many of the core psychotic symptoms, in particular, poor clinical insight. This study aimed to investigate verbal self-monitoring related neural substrates of preserved and poor clinical insight in schizophrenia. It involved 40 stable schizophrenia outpatients, 20 with preserved and 20 with poor insight, and 20 healthy participants. All participants underwent functional magnetic resonance imaging with brain coverage covering key areas in the self-monitoring network during a verbal self-monitoring task. Healthy participants showed higher performance accuracy and greater thalamic activity than both preserved and poor insight patient groups. Preserved insight patients showed higher activity in the putamen extending into the caudate, insula and inferior frontal gyrus, compared to poor insight patients, and in the anterior cingulate and medial frontal gyrus, compared to healthy participants. Poor insight patients did not show greater activity in any brain area compared to preserved insight patients or healthy participants. Future studies may pursue therapeutic avenues, such as meta-cognitive therapies to promote self-monitoring or targeted stimulation of relevant brain areas, as means of enhancing insight in schizophrenia. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Insightfulness and later infant attachment in clinically depressed and nonclinical mothers.

PubMed

Ramsauer, Brigitte; Lotzin, Annett; Quitmann, Julia H; Becker-Stoll, Fabienne; Tharner, Anne; Romer, Georg

2014-01-01

The aim of this pilot study was to investigate the relationship between maternal insightfulness and sensitivity and subsequent infant attachment security and disorganization in clinically depressed and nonclinical mother-infant groups. Nineteen depressed mothers with infants ages 3 to 11 months participated in this study. Twenty nonclinical mother-infant dyads were matched to the clinical sample according to infant sex and age. Maternal depression was assessed using the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (American Psychiatric Association, 1994), insightfulness using the Insightfulness Assessment (IA), and sensitivity using the Maternal Sensitivity Scales (M.D.S. Ainsworth, 1969). IA classifications and subscales were considered separately. Later infant attachment was assessed by the Strange Situation Procedure (M.D.S. Ainsworth, M.C. Blehar, E. Waters, & S. Wall, 1978). Depressed mothers tended to have less securely attached children than did nonclinical mothers. Within the clinical sample, the insightfulness categories correlated slightly moderately with attachment security, but were not related to attachment disorganization. Within the nonclinical sample, the IA categories were slightly moderately associated with attachment security and with disorganization. On IA subscales, relationship patterns differed in clinically depressed and nonclinical mother-infant dyads. These findings provide the first evidence of the predictive power of the IA categorization and subscales on subsequent infant attachment. They also may allow the development of different foci of intervention for enhancing insightful caregiving. © 2014 Michigan Association for Infant Mental Health.

Development of Novel Patient-Derived Xenografts from Breast Cancer Brain Metastases

PubMed Central

Contreras-Zárate, María J.; Ormond, D. Ryan; Gillen, Austin E.; Hanna, Colton; Day, Nicole L.; Serkova, Natalie J.; Jacobsen, Britta M.; Edgerton, Susan M.; Thor, Ann D.; Borges, Virginia F.; Lillehei, Kevin O.; Graner, Michael W.; Kabos, Peter; Cittelly, Diana M.

2017-01-01

Brain metastases are an increasing burden among breast cancer patients, particularly for those with HER2+ and triple negative (TN) subtypes. Mechanistic insight into the pathophysiology of brain metastases and preclinical validation of therapies has relied almost exclusively on intracardiac injection of brain-homing cells derived from highly aggressive TN MDA-MB-231 and HER2+ BT474 breast cancer cell lines. Yet, these well characterized models are far from representing the tumor heterogeneity observed clinically and, due to their fast progression in vivo, their suitability to validate therapies for established brain metastasis remains limited. The goal of this study was to develop and characterize novel human brain metastasis breast cancer patient-derived xenografts (BM-PDXs) to study the biology of brain metastasis and to serve as tools for testing novel therapeutic approaches. We obtained freshly resected brain metastases from consenting donors with breast cancer. Tissue was immediately implanted in the mammary fat pad of female immunocompromised mice and expanded as BM-PDXs. Brain metastases from 3/4 (75%) TN, 1/1 (100%) estrogen receptor positive (ER+), and 5/9 (55.5%) HER2+ clinical subtypes were established as transplantable BM-PDXs. To facilitate tracking of metastatic dissemination using BM-PDXs, we labeled PDX-dissociated cells with EGFP-luciferase followed by reimplantation in mice, and generated a BM-derived cell line (F2-7). Immunohistologic analyses demonstrated that parental and labeled BM-PDXs retained expression of critical clinical markers such as ER, progesterone receptor, epidermal growth factor receptor, HER2, and the basal cell marker cytokeratin 5. Similarly, RNA sequencing analysis showed clustering of parental, labeled BM-PDXs and their corresponding cell line derivative. Intracardiac injection of dissociated cells from BM-E22-1, resulted in magnetic resonance imaging-detectable macrometastases in 4/8 (50%) and micrometastases (8/8) (100%) mice, suggesting that BM-PDXs remain capable of colonizing the brain at high frequencies. Brain metastases developed 8–12 weeks after ic injection, located to the brain parenchyma, grew around blood vessels, and elicited astroglia activation characteristic of breast cancer brain metastasis. These novel BM-PDXs represent heterogeneous and clinically relevant models to study mechanisms of brain metastatic colonization, with the added benefit of a slower progression rate that makes them suitable for preclinical testing of drugs in therapeutic settings. PMID:29164052

Students' approaches to learning in a clinical practicum: A psychometric evaluation based on item response theory.

PubMed

Zhao, Yue; Kuan, Hoi Kei; Chung, Joyce O K; Chan, Cecilia K Y; Li, William H C

2018-07-01

The investigation of learning approaches in the clinical workplace context has remained an under-researched area. Despite the validation of learning approach instruments and their applications in various clinical contexts, little is known about the extent to which an individual item, that reflects a specific learning strategy and motive, effectively contributes to characterizing students' learning approaches. This study aimed to measure nursing students' approaches to learning in a clinical practicum using the Approaches to Learning at Work Questionnaire (ALWQ). Survey research design was used in the study. A sample of year 3 nursing students (n = 208) who undertook a 6-week clinical practicum course participated in the study. Factor analyses were conducted, followed by an item response theory analysis, including model assumption evaluation (unidimensionality and local independence), item calibration and goodness-of-fit assessment. Two subscales, deep and surface, were derived. Findings suggested that: (a) items measuring the deep motive from intrinsic interest and deep strategies of relating new ideas to similar situations, and that of concept mapping served as the strongest discriminating indicators; (b) the surface strategy of memorizing facts and details without an overall picture exhibited the highest discriminating power among all surface items; and, (c) both subscales appeared to be informative in assessing a broad range of the corresponding latent trait. The 21-item ALWQ derived from this study presented an efficient, internally consistent and precise measure. Findings provided a useful psychometric evaluation of the ALWQ in the clinical practicum context, added evidence to the utility of the ALWQ for nursing education practice and research, and echoed the discussions from previous studies on the role of the contextual factors in influencing student choices of different learning strategies. They provided insights for clinical educators to measure nursing students' approaches to learning and facilitate their learning in the clinical practicum setting. Copyright © 2018. Published by Elsevier Ltd.

Understanding latent structures of clinical information logistics: A bottom-up approach for model building and validating the workflow composite score.

PubMed

Esdar, Moritz; Hübner, Ursula; Liebe, Jan-David; Hüsers, Jens; Thye, Johannes

2017-01-01

Clinical information logistics is a construct that aims to describe and explain various phenomena of information provision to drive clinical processes. It can be measured by the workflow composite score, an aggregated indicator of the degree of IT support in clinical processes. This study primarily aimed to investigate the yet unknown empirical patterns constituting this construct. The second goal was to derive a data-driven weighting scheme for the constituents of the workflow composite score and to contrast this scheme with a literature based, top-down procedure. This approach should finally test the validity and robustness of the workflow composite score. Based on secondary data from 183 German hospitals, a tiered factor analytic approach (confirmatory and subsequent exploratory factor analysis) was pursued. A weighting scheme, which was based on factor loadings obtained in the analyses, was put into practice. We were able to identify five statistically significant factors of clinical information logistics that accounted for 63% of the overall variance. These factors were "flow of data and information", "mobility", "clinical decision support and patient safety", "electronic patient record" and "integration and distribution". The system of weights derived from the factor loadings resulted in values for the workflow composite score that differed only slightly from the score values that had been previously published based on a top-down approach. Our findings give insight into the internal composition of clinical information logistics both in terms of factors and weights. They also allowed us to propose a coherent model of clinical information logistics from a technical perspective that joins empirical findings with theoretical knowledge. Despite the new scheme of weights applied to the calculation of the workflow composite score, the score behaved robustly, which is yet another hint of its validity and therefore its usefulness. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Effective Hypothermic Storage of Human Pluripotent Stem Cell-Derived Cardiomyocytes Compatible With Global Distribution of Cells for Clinical Applications and Toxicology Testing

PubMed Central

Correia, Cláudia; Koshkin, Alexey; Carido, Madalena; Espinha, Nuno; Šarić, Tomo; Lima, Pedro A.; Alves, Paula M.

2016-01-01

To fully explore the potential of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs), efficient methods for storage and shipment of these cells are required. Here, we evaluated the feasibility to cold store monolayers and aggregates of functional CMs obtained from different PSC lines using a fully defined clinical-compatible preservation formulation and investigated the time frame that hPSC-CMs could be subjected to hypothermic storage. We showed that two-dimensional (2D) monolayers of hPSC-CMs can be efficiently stored at 4°C for 3 days without compromising cell viability. However, cell viability decreased when the cold storage interval was extended to 7 days. We demonstrated that hPSC-CMs are more resistant to prolonged hypothermic storage-induced cell injury in three-dimensional aggregates than in 2D monolayers, showing high cell recoveries (>70%) after 7 days of storage. Importantly, hPSC-CMs maintained their typical (ultra)structure, gene and protein expression profile, electrophysiological profiles, and drug responsiveness. Significance The applicability of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) in the clinic/industry is highly dependent on the development of efficient methods for worldwide shipment of these cells. This study established effective clinically compatible strategies for cold (4°C) storage of hPSC-CMs cultured as two-dimensional (2D) monolayers and three-dimensional (3D) aggregates. Cell recovery of 2D monolayers of hPSC-CMs was found to be dependent on the time of storage, and 3D cell aggregates were more resistant to prolonged cold storage than 2D monolayers. Of note, it was demonstrated that 7 days of cold storage did not affect hPSC-CM ultrastructure, phenotype, or function. This study provides important insights into the cold preservation of PSC-CMs that could be valuable in improving global commercial distribution of hPSC-CMs. PMID:27025693

Effective Hypothermic Storage of Human Pluripotent Stem Cell-Derived Cardiomyocytes Compatible With Global Distribution of Cells for Clinical Applications and Toxicology Testing.

PubMed

Correia, Cláudia; Koshkin, Alexey; Carido, Madalena; Espinha, Nuno; Šarić, Tomo; Lima, Pedro A; Serra, Margarida; Alves, Paula M

2016-05-01

To fully explore the potential of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs), efficient methods for storage and shipment of these cells are required. Here, we evaluated the feasibility to cold store monolayers and aggregates of functional CMs obtained from different PSC lines using a fully defined clinical-compatible preservation formulation and investigated the time frame that hPSC-CMs could be subjected to hypothermic storage. We showed that two-dimensional (2D) monolayers of hPSC-CMs can be efficiently stored at 4°C for 3 days without compromising cell viability. However, cell viability decreased when the cold storage interval was extended to 7 days. We demonstrated that hPSC-CMs are more resistant to prolonged hypothermic storage-induced cell injury in three-dimensional aggregates than in 2D monolayers, showing high cell recoveries (>70%) after 7 days of storage. Importantly, hPSC-CMs maintained their typical (ultra)structure, gene and protein expression profile, electrophysiological profiles, and drug responsiveness. The applicability of human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) in the clinic/industry is highly dependent on the development of efficient methods for worldwide shipment of these cells. This study established effective clinically compatible strategies for cold (4°C) storage of hPSC-CMs cultured as two-dimensional (2D) monolayers and three-dimensional (3D) aggregates. Cell recovery of 2D monolayers of hPSC-CMs was found to be dependent on the time of storage, and 3D cell aggregates were more resistant to prolonged cold storage than 2D monolayers. Of note, it was demonstrated that 7 days of cold storage did not affect hPSC-CM ultrastructure, phenotype, or function. This study provides important insights into the cold preservation of PSC-CMs that could be valuable in improving global commercial distribution of hPSC-CMs. ©AlphaMed Press.

Structural and functional screening in human induced-pluripotent stem cell-derived cardiomyocytes accurately identifies cardiotoxicity of multiple drug types

DOE Office of Scientific and Technical Information (OSTI.GOV)

Doherty, Kimberly R., E-mail: kimberly.doherty@quintiles.com; Talbert, Dominique R.; Trusk, Patricia B.

Safety pharmacology studies that evaluate new drug entities for potential cardiac liability remain a critical component of drug development. Current studies have shown that in vitro tests utilizing human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CM) may be beneficial for preclinical risk evaluation. We recently demonstrated that an in vitro multi-parameter test panel assessing overall cardiac health and function could accurately reflect the associated clinical cardiotoxicity of 4 FDA-approved targeted oncology agents using hiPS-CM. The present studies expand upon this initial observation to assess whether this in vitro screen could detect cardiotoxicity across multiple drug classes with known clinical cardiac risks.more » Thus, 24 drugs were examined for their effect on both structural (viability, reactive oxygen species generation, lipid formation, troponin secretion) and functional (beating activity) endpoints in hiPS-CM. Using this screen, the cardiac-safe drugs showed no effects on any of the tests in our panel. However, 16 of 18 compounds with known clinical cardiac risk showed drug-induced changes in hiPS-CM by at least one method. Moreover, when taking into account the Cmax values, these 16 compounds could be further classified depending on whether the effects were structural, functional, or both. Overall, the most sensitive test assessed cardiac beating using the xCELLigence platform (88.9%) while the structural endpoints provided additional insight into the mechanism of cardiotoxicity for several drugs. These studies show that a multi-parameter approach examining both cardiac cell health and function in hiPS-CM provides a comprehensive and robust assessment that can aid in the determination of potential cardiac liability. - Highlights: • 24 drugs were tested for cardiac liability using an in vitro multi-parameter screen. • Changes in beating activity were the most sensitive in predicting cardiac risk. • Structural effects add in-depth insight towards mechanism of cardiac toxicity. • Testing functional and structural endpoints enhances early cardiac risk assessment.« less

Neurological soft signs in obsessive compulsive disorder with good and poor insight.

PubMed

Karadag, Filiz; Tumkaya, Selim; Kırtaş, Duygu; Efe, Muharrem; Alacam, Hüseyin; Oguzhanoglu, Nalan K

2011-06-01

Obsessive compulsive disorder (OCD) is a clinically heterogeneous disorder; OCD with poor insight has been suggested to be a specific clinical subtype. Neurological soft signs (NSSs) may be helpful to identify the specific subtypes of OCD patients. In the present study, we aimed to compare OCD patients with poor insight with OCD patients having good insight, and healthy individuals. Sixty-four OCD patients (38 with good insight and 26 with poor insight), and 32 healthy subjects were enrolled in the present study. The Overvalued Ideas Scale (OVIS) was used to determine OCD patients with poor insight. NSSs were assessed by using the Neurological Evaluation Scale (NES). Two OCD groups had significantly higher total NES scores compared to controls (p=.000). Compared to healthy controls, OCD patients with poor insight performed significantly worse on all NES subscales, and they had significantly more NSSs on motor coordination, and sensory integration subscales compared to the OCD with good insight group. Our results suggested that OCD patients with poor insight exhibit more extensive neurodevelopmental impairments compared to OCD patients with good insight. Copyright © 2011 Elsevier Inc. All rights reserved.

Bayesian Community Detection in the Space of Group-Level Functional Differences

PubMed Central

Venkataraman, Archana; Yang, Daniel Y.-J.; Pelphrey, Kevin A.; Duncan, James S.

2017-01-01

We propose a unified Bayesian framework to detect both hyper- and hypo-active communities within whole-brain fMRI data. Specifically, our model identifies dense subgraphs that exhibit population-level differences in functional synchrony between a control and clinical group. We derive a variational EM algorithm to solve for the latent posterior distributions and parameter estimates, which subsequently inform us about the afflicted network topology. We demonstrate that our method provides valuable insights into the neural mechanisms underlying social dysfunction in autism, as verified by the Neurosynth meta-analytic database. In contrast, both univariate testing and community detection via recursive edge elimination fail to identify stable functional communities associated with the disorder. PMID:26955022

Bayesian Community Detection in the Space of Group-Level Functional Differences.

PubMed

Venkataraman, Archana; Yang, Daniel Y-J; Pelphrey, Kevin A; Duncan, James S

2016-08-01

We propose a unified Bayesian framework to detect both hyper- and hypo-active communities within whole-brain fMRI data. Specifically, our model identifies dense subgraphs that exhibit population-level differences in functional synchrony between a control and clinical group. We derive a variational EM algorithm to solve for the latent posterior distributions and parameter estimates, which subsequently inform us about the afflicted network topology. We demonstrate that our method provides valuable insights into the neural mechanisms underlying social dysfunction in autism, as verified by the Neurosynth meta-analytic database. In contrast, both univariate testing and community detection via recursive edge elimination fail to identify stable functional communities associated with the disorder.

Endothelial-regenerating cells: an expanding universe.

PubMed

Steinmetz, Martin; Nickenig, Georg; Werner, Nikos

2010-03-01

Atherosclerosis is the most common cause for cardiovascular diseases and is based on endothelial dysfunction. A growing body of evidence suggests the contribution of bone marrow-derived endothelial progenitor cells, monocytic cells, and mature endothelial cells to vessel formation and endothelial rejuvenation. To this day, various subsets of these endothelial-regenerating cells have been identified according to cellular origin, phenotype, and properties in vivo and in vitro. However, the definition and biology, especially of endothelial progenitor cells, is complex and under heavy debate. In this review, we focus on current definitions of endothelial progenitor cells, highlight the clinical relevance of endothelial-regenerating cells, and provide new insights into cell-cell interactions involved in endothelial cell rejuvenation.

Oxindole: A chemical prism carrying plethora of therapeutic benefits.

PubMed

Kaur, Maninder; Singh, Manjinder; Chadha, Navriti; Silakari, Om

2016-11-10

Oxindole has emerged as a valuable scaffold in medicinal chemistry possessing diverse range of pharmacological activities. Its value has further been increased by its natural occurrence as alkaloids in variety of plants. It was first extracted from the cat claw's plant Uncaria tomentosa found in the Amazon rainforest and other tropical areas of South and Central America. Traditionally as well as present emerging therapeutic potential of oxindole nucleus has captured the interest of medicinal chemists to synthesize novel oxindole derivatives. In the present review the authors have integrated its chemistry and synthetic strategies developed after 1945. Also the information of naturally occurring oxindole alkaloids has been incorporated. The detailed pharmacological activities including anti-cancer, anti-HIV, antidiabetic, antibacterial, antioxidant, kinase inhibitory, AChE inhibitory, anti-leishmanial, β3 adrenergic receptor agonistic, phosphatase inhibitory, analgesic, spermicidal, vasopressin antagonists, progesterone antagonists, neuroprotection, and NMDA blocker activities of oxindole derivatives alongwith their SAR has also been discussed in detail. Additionally, information regarding the oxindole derivatives in clinical trials has been incorporated. Thus, this review will provide insights for the synthetic as well as medicinal chemist for the designing and synthesis of novel oxindole derivatives with novel improved range of pharmacological implications. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Current Status and Future Prospects of Marine Natural Products (MNPs) as Antimicrobials

PubMed Central

Choudhary, Alka; Naughton, Lynn M.; Montánchez, Itxaso

2017-01-01

The marine environment is a rich source of chemically diverse, biologically active natural products, and serves as an invaluable resource in the ongoing search for novel antimicrobial compounds. Recent advances in extraction and isolation techniques, and in state-of-the-art technologies involved in organic synthesis and chemical structure elucidation, have accelerated the numbers of antimicrobial molecules originating from the ocean moving into clinical trials. The chemical diversity associated with these marine-derived molecules is immense, varying from simple linear peptides and fatty acids to complex alkaloids, terpenes and polyketides, etc. Such an array of structurally distinct molecules performs functionally diverse biological activities against many pathogenic bacteria and fungi, making marine-derived natural products valuable commodities, particularly in the current age of antimicrobial resistance. In this review, we have highlighted several marine-derived natural products (and their synthetic derivatives), which have gained recognition as effective antimicrobial agents over the past five years (2012–2017). These natural products have been categorized based on their chemical structures and the structure-activity mediated relationships of some of these bioactive molecules have been discussed. Finally, we have provided an insight into how genome mining efforts are likely to expedite the discovery of novel antimicrobial compounds. PMID:28846659

Modeling neurodegenerative diseases with patient-derived induced pluripotent cells: Possibilities and challenges.

PubMed

Poon, Anna; Zhang, Yu; Chandrasekaran, Abinaya; Phanthong, Phetcharat; Schmid, Benjamin; Nielsen, Troels T; Freude, Kristine K

2017-10-25

The rising prevalence of progressive neurodegenerative diseases coupled with increasing longevity poses an economic burden at individual and societal levels. There is currently no effective cure for the majority of neurodegenerative diseases and disease-affected tissues from patients have been difficult to obtain for research and drug discovery in pre-clinical settings. While the use of animal models has contributed invaluable mechanistic insights and potential therapeutic targets, the translational value of animal models could be further enhanced when combined with in vitro models derived from patient-specific induced pluripotent stem cells (iPSCs) and isogenic controls generated using CRISPR-Cas9 mediated genome editing. The iPSCs are self-renewable and capable of being differentiated into the cell types affected by the diseases. These in vitro models based on patient-derived iPSCs provide the opportunity to model disease development, uncover novel mechanisms and test potential therapeutics. Here we review findings from iPSC-based modeling of selected neurodegenerative diseases, including Alzheimer's disease, frontotemporal dementia and spinocerebellar ataxia. Furthermore, we discuss the possibilities of generating three-dimensional (3D) models using the iPSCs-derived cells and compare their advantages and disadvantages to conventional two-dimensional (2D) models. Copyright © 2017 Elsevier B.V. All rights reserved.

Induced pluripotent stem cell-derived cardiomyocytes for cardiovascular disease modeling and drug screening.

PubMed

Sharma, Arun; Wu, Joseph C; Wu, Sean M

2013-12-24

Human induced pluripotent stem cells (hiPSCs) have emerged as a novel tool for drug discovery and therapy in cardiovascular medicine. hiPSCs are functionally similar to human embryonic stem cells (hESCs) and can be derived autologously without the ethical challenges associated with hESCs. Given the limited regenerative capacity of the human heart following myocardial injury, cardiomyocytes derived from hiPSCs (hiPSC-CMs) have garnered significant attention from basic and translational scientists as a promising cell source for replacement therapy. However, ongoing issues such as cell immaturity, scale of production, inter-line variability, and cell purity will need to be resolved before human clinical trials can begin. Meanwhile, the use of hiPSCs to explore cellular mechanisms of cardiovascular diseases in vitro has proven to be extremely valuable. For example, hiPSC-CMs have been shown to recapitulate disease phenotypes from patients with monogenic cardiovascular disorders. Furthermore, patient-derived hiPSC-CMs are now providing new insights regarding drug efficacy and toxicity. This review will highlight recent advances in utilizing hiPSC-CMs for cardiac disease modeling in vitro and as a platform for drug validation. The advantages and disadvantages of using hiPSC-CMs for drug screening purposes will be explored as well.

Relationship between insight and theory of mind in schizophrenia: A meta-analysis.

PubMed

Bora, Emre

2017-12-01

Poor insight in schizophrenia has been associated with executive dysfunction and deficits in general cognitive ability. The overall outcome of available neurocognitive studies suggests that there is a significant but modest relationship between cognitive deficits and poor insight in schizophrenia. However, social cognitive abilities, particularly, theory of mind (ToM), might also play a role in poor insight in schizophrenia. A novel meta-analysis of the relationship between ToM and insight in schizophrenia was conducted. Current meta-analysis included 16 studies including 1085 patients with schizophrenia-spectrum disorders. There was a significant association between ToM and clinical insight (r=0.28, CI=0.20-0.36). By contrast, there was no significant relationship between ToM and cognitive insight. Current findings suggest that there is a small but significant relationship between ToM and clinical insight in schizophrenia. ToM impairment is one of the factors contributing to poor insight in schizophrenia. Copyright © 2017 Elsevier B.V. All rights reserved.

Verification of computed tomographic estimates of cochlear implant array position: a micro-CT and histologic analysis.

PubMed

Teymouri, Jessica; Hullar, Timothy E; Holden, Timothy A; Chole, Richard A

2011-08-01

To determine the efficacy of clinical computed tomographic (CT) imaging to verify postoperative electrode array placement in cochlear implant (CI) patients. Nine fresh cadaver heads underwent clinical CT scanning, followed by bilateral CI insertion and postoperative clinical CT scanning. Temporal bones were removed, trimmed, and scanned using micro-CT. Specimens were then dehydrated, embedded in either methyl methacrylate or LR White resin, and sectioned with a diamond wafering saw. Histology sections were examined by 3 blinded observers to determine the position of individual electrodes relative to soft tissue structures within the cochlea. Electrodes were judged to be within the scala tympani, scala vestibuli, or in an intermediate position between scalae. The position of the array could be estimated accurately from clinical CT scans in all specimens using micro-CT and histology as a criterion standard. Verification using micro-CT yielded 97% agreement, and histologic analysis revealed 95% agreement with clinical CT results. A composite, 3-dimensional image derived from a patient's preoperative and postoperative CT images using a clinical scanner accurately estimates the position of the electrode array as determined by micro-CT imaging and histologic analyses. Information obtained using the CT method provides valuable insight into numerous variables of interest to patient performance such as surgical technique, array design, and processor programming and troubleshooting.

A study of poor insight in social anxiety disorder.

PubMed

Vigne, Paula; de Menezes, Gabriela B; Harrison, Ben J; Fontenelle, Leonardo F

2014-11-30

We investigated levels of insight among patients with Social Anxiety Disorder (SAD) as compared to patients with Obsessive-Compulsive Disorder (OCD) and evaluated whether levels of insight in SAD were related to specific sociodemographic and/or clinical features. Thirty-seven SAD patients and 51 OCD patients attending a tertiary obsessive-compulsive and anxiety disorders clinic were assessed with a sociodemographic and clinical questionnaire, a structured diagnostic interview, the Brown Assessment of Beliefs Scale (BABS), the Social Phobia Inventory (SPIN), the Beck Depression Inventory (BDI), the Sheehan Disability Scale (SDS), and the Treatment Adherence Survey-patient version (TAS-P). According to the BABS, SAD patients exhibited insight levels that were as low as those exhibited by OCD patients, with up to 29.7% of them being described as "poor insight" SAD. Although poor insight SAD patients were more frequently married, less depressed and displayed a statistical trend towards greater rates of early drop-out from cognitive-behavioral therapy, their insight levels were not associated with other variables of interest, including sex, age, employment, age at onset, duration of illness, associated psychiatric disorders, SPIN and SDS scores. Patients with poor insight SAD might perceive their symptoms as being less distressful and thus report fewer depressive symptoms and high rates of treatment non-adherence. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Behavioral Economics: A New Lens for Understanding Genomic Decision Making.

PubMed

Moore, Scott Emory; Ulbrich, Holley H; Hepburn, Kenneth; Holaday, Bonnie; Mayo, Rachel; Sharp, Julia; Pruitt, Rosanne H

2018-05-01

This article seeks to take the next step in examining the insights that nurses and other healthcare providers can derive from applying behavioral economic concepts to support genomic decision making. As genomic science continues to permeate clinical practice, nurses must continue to adapt practice to meet new challenges. Decisions associated with genomics are often not simple and dichotomous in nature. They can be complex and challenging for all involved. This article offers an introduction to behavioral economics as a possible tool to help support patients', families', and caregivers' decision making related to genomics. Using current writings from nursing, ethics, behavioral economic, and other healthcare scholars, we review key concepts of behavioral economics and discuss their relevance to supporting genomic decision making. Behavioral economic concepts-particularly relativity, deliberation, and choice architecture-are specifically examined as new ways to view the complexities of genomic decision making. Each concept is explored through patient decision making and clinical practice examples. This article also discusses next steps and practice implications for further development of the behavioral economic lens in nursing. Behavioral economics provides valuable insight into the unique nature of genetic decision-making practices. Nurses are often a source of information and support for patients during clinical decision making. This article seeks to offer behavioral economic concepts as a framework for understanding and examining the unique nature of genomic decision making. As genetic and genomic testing become more common in practice, it will continue to grow in importance for nurses to be able to support the autonomous decision making of patients, their families, and caregivers. © 2018 Sigma Theta Tau International.

Parental insightfulness: retrospect and prospect.

PubMed

Koren-Karie, Nina; Oppenheim, David

2018-06-01

We open this introductory paper to the special issue with the theoretical and clinical roots of the insightfulness concept. Next, the Insightfulness Assessment (IA) is presented, followed by a review of key empirical findings supporting the IA. The central points in the papers in this special issue are reviewed next. These include the use of the IA with parents of children ranging in age from infancy to adolescence, its applicability outside the parent-child relationship (e.g. insightfulness toward a close friend), its use with high-risk mothers, and the usefulness of insightfulness both as a continuous and a categorical measure. The clinical applications of the IA are discussed, and we close with future directions for IA research.

Natural Products: Insights into Leishmaniasis Inflammatory Response

PubMed Central

Rodrigues, Igor A.; Mazotto, Ana Maria; Cardoso, Verônica; Alves, Renan L.; Amaral, Ana Claudia F.; Silva, Jefferson Rocha de Andrade; Pinheiro, Anderson S.; Vermelho, Alane B.

2015-01-01

Leishmaniasis is a vector-borne disease that affects several populations worldwide, against which there are no vaccines available and the chemotherapy is highly toxic. Depending on the species causing the infection, the disease is characterized by commitment of tissues, including the skin, mucous membranes, and internal organs. Despite the relevance of host inflammatory mediators on parasite burden control, Leishmania and host immune cells interaction may generate an exacerbated proinflammatory response that plays an important role in the development of leishmaniasis clinical manifestations. Plant-derived natural products have been recognized as bioactive agents with several properties, including anti-protozoal and anti-inflammatory activities. The present review focuses on the antileishmanial activity of plant-derived natural products that are able to modulate the inflammatory response in vitro and in vivo. The capability of crude extracts and some isolated substances in promoting an anti-inflammatory response during Leishmania infection may be used as part of an effective strategy to fight the disease. PMID:26538837

Research with parthenogenetic stem cells will help decide whether a safer clinical use is possible.

PubMed

Muñoz, M; Penarossa, G; Caamaño, J N; Díez, C; Brevini, T A L; Gómez, E

2015-04-01

The derivation and use of parthenogenetic stem cells (pESCs) are envisaged as a reliable alternative to conventional embryonic stem cells. Similar to embryonic stem cells in their proliferation, expression of pluripotency markers and capacity to multilineage differentiation, pESCs are at a lower risk of immune rejection within stem cell-based therapeutics. Moreover, pESCs represent an important model system to study the effect of paternally imprinted genes on cell differentiation. However, currently available information about the genetic and epigenetic behaviour of pESCs is limited. Thus, a detailed look at the biology of parthenogenetic (PG) embryos and PG-derived cell lines would allow gaining insight into the full potential of pESC in biotechnology. In this commentary article we review some features related to the biology of PG embryos and pESCs. In addition, novel traits on bovine pESCs (bpESCs) are discussed. Copyright © 2013 John Wiley & Sons, Ltd.

Characterization of Reemerging Chikungunya Virus

PubMed Central

Sourisseau, Marion; Schilte, Clémentine; Casartelli, Nicoletta; Trouillet, Céline; Guivel-Benhassine, Florence; Rudnicka, Dominika; Sol-Foulon, Nathalie; Roux, Karin Le; Prevost, Marie-Christine; Fsihi, Hafida; Frenkiel, Marie-Pascale; Blanchet, Fabien; Afonso, Philippe V; Ceccaldi, Pierre-Emmanuel; Ozden, Simona; Gessain, Antoine; Schuffenecker, Isabelle; Verhasselt, Bruno; Zamborlini, Alessia; Saïb, Ali; Rey, Felix A; Arenzana-Seisdedos, Fernando; Desprès, Philippe; Michault, Alain; Albert, Matthew L; Schwartz, Olivier

2007-01-01

An unprecedented epidemic of chikungunya virus (CHIKV) infection recently started in countries of the Indian Ocean area, causing an acute and painful syndrome with strong fever, asthenia, skin rash, polyarthritis, and lethal cases of encephalitis. The basis for chikungunya disease and the tropism of CHIKV remain unknown. Here, we describe the replication characteristics of recent clinical CHIKV strains. Human epithelial and endothelial cells, primary fibroblasts and, to a lesser extent, monocyte-derived macrophages, were susceptible to infection and allowed viral production. In contrast, CHIKV did not replicate in lymphoid and monocytoid cell lines, primary lymphocytes and monocytes, or monocyte-derived dendritic cells. CHIKV replication was cytopathic and associated with an induction of apoptosis in infected cells. Chloroquine, bafilomycin-A1, and short hairpin RNAs against dynamin-2 inhibited viral production, indicating that viral entry occurs through pH-dependent endocytosis. CHIKV was highly sensitive to the antiviral activity of type I and II interferons. These results provide a general insight into the interaction between CHIKV and its mammalian host. PMID:17604450

The Impact of the Brain-Derived Neurotrophic Factor Gene on Trauma and Spatial Processing.

PubMed

Miller, Jessica K; McDougall, Siné; Thomas, Sarah; Wiener, Jan

2017-11-27

The influence of genes and the environment on the development of Post-Traumatic Stress Disorder (PTSD) continues to motivate neuropsychological research, with one consistent focus being the Brain-Derived Neurotrophic Factor (BDNF) gene, given its impact on the integrity of the hippocampal memory system. Research into human navigation also considers the BDNF gene in relation to hippocampal dependent spatial processing. This speculative paper brings together trauma and spatial processing for the first time and presents exploratory research into their interactions with BDNF. We propose that quantifying the impact of BDNF on trauma and spatial processing is critical and may well explain individual differences in clinical trauma treatment outcomes and in navigation performance. Research has already shown that the BDNF gene influences PTSD severity and prevalence as well as navigation behaviour. However, more data are required to demonstrate the precise hippocampal dependent processing mechanisms behind these influences in different populations and environmental conditions. This paper provides insight from recent studies and calls for further research into the relationship between allocentric processing, trauma processing and BDNF. We argue that research into these neural mechanisms could transform PTSD clinical practice and professional support for individuals in trauma-exposing occupations such as emergency response, law enforcement and the military.

Jackknife variance of the partial area under the empirical receiver operating characteristic curve.

PubMed

Bandos, Andriy I; Guo, Ben; Gur, David

2017-04-01

Receiver operating characteristic analysis provides an important methodology for assessing traditional (e.g., imaging technologies and clinical practices) and new (e.g., genomic studies, biomarker development) diagnostic problems. The area under the clinically/practically relevant part of the receiver operating characteristic curve (partial area or partial area under the receiver operating characteristic curve) is an important performance index summarizing diagnostic accuracy at multiple operating points (decision thresholds) that are relevant to actual clinical practice. A robust estimate of the partial area under the receiver operating characteristic curve is provided by the area under the corresponding part of the empirical receiver operating characteristic curve. We derive a closed-form expression for the jackknife variance of the partial area under the empirical receiver operating characteristic curve. Using the derived analytical expression, we investigate the differences between the jackknife variance and a conventional variance estimator. The relative properties in finite samples are demonstrated in a simulation study. The developed formula enables an easy way to estimate the variance of the empirical partial area under the receiver operating characteristic curve, thereby substantially reducing the computation burden, and provides important insight into the structure of the variability. We demonstrate that when compared with the conventional approach, the jackknife variance has substantially smaller bias, and leads to a more appropriate type I error rate of the Wald-type test. The use of the jackknife variance is illustrated in the analysis of a data set from a diagnostic imaging study.

Structural insight into the active site of mushroom tyrosinase using phenylbenzoic acid derivatives.

PubMed

Oyama, Takahiro; Yoshimori, Atsushi; Takahashi, Satoshi; Yamamoto, Tetsuya; Sato, Akira; Kamiya, Takanori; Abe, Hideaki; Abe, Takehiko; Tanuma, Sei-Ichi

2017-07-01

So far, many inhibitors of tyrosinase have been discovered for cosmetic and clinical agents. However, the molecular mechanisms underlying the inhibition in the active site of tyrosinase have not been well understood. To explore this problem, we examined here the inhibitory effects of 4'-hydroxylation and methoxylation of phenylbenzoic acid (PBA) isomers, which have a unique scaffold to inhibit mushroom tyrosinase. The inhibitory effect of 3-PBA, which has the most potent inhibitory activity among the isomers, was slightly decreased by 4'-hydroxylation and further decreased by 4'-methoxylation against mushroom tyrosinase. Surprisingly, 4'-hydroxylation but not methoxylation of 2-PBA appeared inhibitory activity. On the other hand, both 4'-hydroxylation and methoxylation of 4-PBA increased the inhibitory activity against mushroom tyrosinase. In silico docking analyses using the crystallographic structure of mushroom tyrosinase indicated that the carboxylic acid or 4'-hydroxyl group of PBA derivatives could chelate with cupric ions in the active site of mushroom tyrosinase, and that the interactions of Asn260 and Phe264 in the active site with the adequate-angled biphenyl group are involved in the inhibitory activities of the modified PBAs, by parallel and T-shaped π-π interactions, respectively. Furthermore, Arg268 could fix the angle of the aromatic ring of Phe264, and Val248 is supposed to interact with the inhibitors as a hydrophobic manner. These results may enhance the structural insight into mushroom tyrosinase for the creation of novel tyrosinase inhibitors. Copyright © 2017 Elsevier Ltd. All rights reserved.

Clinical reasoning-embodied meaning-making in physiotherapy.

PubMed

Chowdhury, Anoop; Bjorbækmo, Wenche Schrøder

2017-07-01

This article examines physiotherapists' lived experience of practicing physiotherapy in primary care, focusing on clinical reasoning and decision-making in the case of a patient we call Eva. The material presented derives from a larger study involving two women participants, both with a protracted history of neck and shoulder pain. A total of eight sessions, all of them conducted by the first author, a professional physiotherapist, in his own practice room, were videotaped, after which the first author transcribed the sessions and added reflective notes. One session emerged as particularly stressful for both parties and is explored in detail in this article. In our analysis, we seek to be attentive to the experiences of physiotherapy displayed and to explore their meaning, significance and uniqueness from a phenomenological perspective. Our research reveals the complexity of integrating multiple theoretical perspectives of practice in clinical decision-making and suggests that a phenomenological perspective can provide insights into clinical encounters through its recognition of embodied knowledge. We argue that good physiotherapy practice demands tactfulness, sensitivity, and the desire to build a cooperative patient-therapist relationship. Informed by theoretical and practical knowledge from multiple disciplines, patient management can evolve and unfold beyond rehearsed routines and theoretical principles.

Toward integrated management of cerebral aneurysms.

PubMed

Villa-Uriol, M C; Larrabide, I; Pozo, J M; Kim, M; Camara, O; De Craene, M; Zhang, C; Geers, A J; Morales, H; Bogunović, H; Cardenes, R; Frangi, A F

2010-06-28

In the last few years, some of the visionary concepts behind the virtual physiological human began to be demonstrated on various clinical domains, showing great promise for improving healthcare management. In the current work, we provide an overview of image- and biomechanics-based techniques that, when put together, provide a patient-specific pipeline for the management of intracranial aneurysms. The derivation and subsequent integration of morphological, morphodynamic, haemodynamic and structural analyses allow us to extract patient-specific models and information from which diagnostic and prognostic descriptors can be obtained. Linking such new indices with relevant clinical events should bring new insights into the processes behind aneurysm genesis, growth and rupture. The development of techniques for modelling endovascular devices such as stents and coils allows the evaluation of alternative treatment scenarios before the intervention takes place and could also contribute to the understanding and improved design of more effective devices. A key element to facilitate the clinical take-up of all these developments is their comprehensive validation. Although a number of previously published results have shown the accuracy and robustness of individual components, further efforts should be directed to demonstrate the diagnostic and prognostic efficacy of these advanced tools through large-scale clinical trials.

Meeting report of the International Consortium of Stem Cell Networks' Workshop Towards Clinical Trials Using Stem Cells for Amyotrophic Lateral Sclerosis/Motor Neuron Disease.

PubMed

Chaddah, Maya R; Dickie, Brian G; Lyall, Drew; Marshall, Caroline J; Sykes, J Ben; Bruijn, Lucie I

2011-09-01

The International Consortium of Stem Cell Networks' (ICSCN) Workshop Towards Clinical Trials Using Stem Cells for Amyotrophic Lateral Sclerosis (ALS)/Motor Neuron Disease (MND) was held on 24-25 January 2011. Twenty scientific talks addressed aspects of cell derivation and characterization; preclinical research and phased clinical trials involving stem cells; latest developments in induced pluripotent (iPS) cell technology; industry involvement and investment. Three moderated panel discussions focused on unregulated ALS/MND treatments, and the state of the art and barriers to future progress in using stem cells for ALS/MND. This review highlights the major insights that emanated from the workshop around the lessons learned and barriers to progress for using stem cells for understanding disease mechanism, drug discovery, and as therapy for ALS/MND. The full meeting report is only available in the online version of the journal. Please find this material with the following direct link to the article: http://www.informahealthcare.com/als/doi/10.3109/17482968.2011.590992 .

Experiences of undergraduate African health sciences students: A hermeneutic inquiry.

PubMed

Inyama, Davis; Williams, Allison; McCauley, Kay

2015-06-01

While efforts have been made to understand the experiences of African students in predominantly white environments, the experiences of African students in clinical placement areas have rarely been explored. This paper is a report on a study designed to address the gap in educational research on the experiences of African health sciences students in clinical placements in predominantly white environments. Interviews adopting an open approach to conversations were conducted with nine African students from three health disciplines at one metropolitan university in Australia between 2012 and 2013. Interview transcripts were analyzed using philosophical hermeneutics, where shared meanings were arrived at by employing key Gadamerian hermeneutic components. Findings revealed a number of factors that had a direct effect on the meaning students derived from their clinical placement experiences. These, as revealed in the interlinked domains of body, space, relationships, and time included difference, acceptance, resilience, and cultural sensitivity. Insights from this study may lead to the adoption of strategies designed to improve the experiences of African students studying health sciences in predominantly white environments. © 2014 Wiley Publishing Asia Pty Ltd.

Probing nitrobenzhydrol uncaging mechanisms using FerriCast.

PubMed

Kennedy, Daniel P; Brown, Daniel C; Burdette, Shawn C

2010-10-15

The FerriCast derivative FC-NDBF was synthesized from 3-methyl-2-nitrodibenzofuran (NDBF). The photochemistry of the target Fe(3+) photocage and several related congeners provides mechanistic insight into the uncaging quantum yields of nitrobenzhydrol-derived ligands.

Toward a Model of Cognitive Insight in First-Episode Psychosis: Verbal Memory and Hippocampal Structure

PubMed Central

Buchy, L.; Czechowska, Y.; Chochol, C.; Malla, A.; Joober, R.; Pruessner, J.; Lepage, M.

2010-01-01

Our previous work has linked verbal learning and memory with cognitive insight, but not clinical insight, in individuals with a first-episode psychosis (FEP). The current study reassessed the neurocognitive basis of cognitive and clinical insight and explored their neural basis in 61 FEP patients. Cognitive insight was measured with the Beck Cognitive Insight Scale (BCIS) and clinical insight with the Scale to assess Unawareness of Mental Disorder (SUMD). Global measures for 7 domains of cognition were examined. Hippocampi were manually segmented in to 3 parts: the body, head, and tail. Verbal learning and memory significantly correlated with the BCIS composite index. Composite index scores were significantly associated with total left hippocampal (HC) volume; partial correlations, however, revealed that this relationship was attributable largely to verbal memory performance. The BCIS self-certainty subscale significantly and inversely correlated with bilateral HC volumes, and these associations were independent of verbal learning and memory performance. The BCIS self-reflectiveness subscale significantly correlated with verbal learning and memory but not with HC volume. No significant correlations emerged between the SUMD and verbal memory or HC volume. These results strengthen our previous assertion that in individuals with an FEP cognitive insight may rely on memory whereby current experiences are appraised based on previous ones. The HC may be a viable location among others for the brain system that underlies aspects of cognitive insight in individuals with an FEP. PMID:19346315

Development of a Research Participants’ Perception Survey to Improve Clinical Research

PubMed Central

Yessis, Jennifer L.; Kost, Rhonda G.; Lee, Laura M.; Coller, Barry S.; Henderson, David K.

2012-01-01

Abstract Introduction: Clinical research participants’ perceptions regarding their experiences during research protocols provide outcome‐based insights into the effectiveness of efforts to protect rights and safety, and opportunities to enhance participants’ clinical research experiences. Use of validated surveys measuring patient‐centered outcomes is standard in hospitals, yet no instruments exist to assess outcomes of clinical research processes. Methods: We derived survey questions from data obtained from focus groups comprised of research participants and professionals. We assessed the survey for face/content validity, and privacy/confidentiality protections and fielded it to research participants at 15 centers. We conducted analyses of response rates, sample characteristics, and psychometrics, including survey and item completion and analysis, internal consistency, item internal consistency, criterion‐related validity, and item usefulness. Responses were tested for fit into existing patient‐centered dimensions of care and new clinical research dimensions using Cronbach's alpha coefficient. Results: Surveys were mailed to 18,890 individuals; 4,961 were returned (29%). Survey completion was 89% overall; completion rates exceeded 90% for 88 of 93 evaluable items. Questions fit into three dimensions of patient‐centered care and two novel clinical research dimensions (Cronbach's alpha for dimensions: 0.69–0.85). Conclusions: The validated survey offers a new method for assessing and improving outcomes of clinical research processes. Clin Trans Sci 2012; Volume 5: 452–460 PMID:23253666

The relationship between clinical characteristics, metacognitive appraisals, and cognitive insight in patients with obsessive-compulsive disorder.

PubMed

Ekinci, Okan; Ekinci, Asli

2016-11-01

Cognitive insight, a recently developed insight measure, refers to metacognitive processes of the re-evaluation and correction of distorted beliefs and misinterpretations. However, to the best of the authors' knowledge, no study has specifically examined cognitive insight, demographics, psychopathological variables, and distorted beliefs in OCD. The aim of this research was to examine links between cognitive insight and demographics, clinical factors, and distorted beliefs among patients with OCD. Eighty-four consecutive outpatients with a diagnosis of OCD underwent a detailed clinical assessment for OCD, including the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), Beck Cognitive Insight Scale (BCIS), Thought-Action Fusion Scale (TAFS), White Bear Thought Suppression Inventory, Metacognition Questioniarre-30 (MCQ-30), and a sociodemographic questionnaire. In addition, 82 control subjects matched for age, education, and gender were tested. BCIS-self-certainty scores were all substantially higher in subjects with remitted and unremitted OCD than in healthy comparison subjects, while BCIS-composite scores were significantly lower in both patient groups than controls. Obsession and compulsion severity had significant effects on BCIS scores. In addition, it was found that the specific symptoms were linked to self-certainty scores. Self-reflectiveness and composite scores had positive correlations with the sub-scale scores of the MCQ-30, while the TAF-morality score was positively correlated with self-certainty scores. The results demonstrated poor cognitive insight among remitted and unremitted OCD patients. In addition, the present study suggested significant associations between sociodemographic and clinical features and dysfunctional appraisals. Cognitive-behavioural techniques aimed at enhancing cognitive insight may be beneficial for patients with OCD, particularly patients who have prominent dysfunctional beliefs.

Stronger default mode network connectivity is associated with poorer clinical insight in youth at ultra high-risk for psychotic disorders.

PubMed

Clark, Sarah V; Mittal, Vijay A; Bernard, Jessica A; Ahmadi, Aral; King, Tricia Z; Turner, Jessica A

2018-03-01

Impaired clinical insight (CI) is a common symptom of psychotic disorders and a promising treatment target. However, to date, our understanding of how variability in CI is tied to underlying brain dysfunction in the clinical high-risk period is limited. Developing a stronger conception of this link will be a vital first step for efforts to determine if CI can serve as a useful prognostic indicator. The current study investigated whether variability in CI is related to major brain networks in adolescents and young adults at ultra high-risk (UHR) of developing psychosis. Thirty-five UHR youth were administered structured clinical interviews as well as an assessment for CI and underwent resting-state magnetic resonance imaging scans. Functional connectivity was calculated in the default mode network (DMN) and fronto-parietal network (FPN), two major networks that are dysfunctional in psychosis and are hypothesized to affect insight. Greater DMN connectivity between the posterior cingulate/precuneus and ventromedial prefrontal cortex (DMN) was related to poorer CI (R 2 =0.399). There were no significant relationships between insight and the FPN. This is the first study to relate a major brain network to clinical insight before the onset of psychosis. Findings are consistent with evidence if a hyperconnected DMN in schizophrenia and UHR, and similar to a previous study of insight and connectivity in schizophrenia. Results suggest that a strongly connected DMN may be related to poor self-awareness of subthreshold psychotic symptoms in UHR adolescents and young adults. Copyright © 2017 Elsevier B.V. All rights reserved.

Improving cognitive outcome in cerebral malaria: insights from clinical and experimental research.

PubMed

de Miranda, Aline Silva; Brant, Fátima; Machado, Fabiana Simão; Rachid, Milene Alvarenga; Teixeira, Antônio Lúcio

2011-12-01

Cerebral Malaria (CM) is a clinical syndrome defined by the World Health Organization (WHO) as a potentially reversible diffuse encephalopathy characterized mainly by coma and the presence of asexual forms of Plasmodium falciparum parasites in peripheral blood smears in the absence of other causes of encephalopathy. A wide range of clinical manifestations follows the disease including cognitive, behavioral and motor dysfunctions, seizures and coma. The underlying mechanisms of CM pathogenesis remain incompletely understood although vascular, immunological and metabolic changes have been described. The classical treatment of CM is based on the administration of antimalarial drugs, especially chloroquine and artemisinin derivates as artesunate. Even with treatment, 15 to 20% of children with CM die and approximately 10 to 17% of those who survive remain with significant long-term cognitive impairment. In this context, neuroprotective and adjuvant therapies have been recently investigated in clinical and experimental studies of CM in an attempt to improve cognitive outcome. A poor understanding of pathophysiological mechanisms, properties of compounds used and patient selection have contributed to the lack of success of these interventions. This review discusses clinical aspects of cognitive sequelae, possible mechanisms involved in the brain injury, perspectives and limitations regarding the pharmacological strategies to improve cognitive outcome in CM.

Integrative topological analysis of mass spectrometry data reveals molecular features with clinical relevance in esophageal squamous cell carcinoma

PubMed Central

Gao, She-Gan; Liu, Rui-Min; Zhao, Yun-Gang; Wang, Pei; Ward, Douglas G.; Wang, Guang-Chao; Guo, Xiang-Qian; Gu, Juan; Niu, Wan-Bin; Zhang, Tian; Martin, Ashley; Guo, Zhi-Peng; Feng, Xiao-Shan; Qi, Yi-Jun; Ma, Yuan-Fang

2016-01-01

Combining MS-based proteomic data with network and topological features of such network would identify more clinically relevant molecules and meaningfully expand the repertoire of proteins derived from MS analysis. The integrative topological indexes representing 95.96% information of seven individual topological measures of node proteins were calculated within a protein-protein interaction (PPI) network, built using 244 differentially expressed proteins (DEPs) identified by iTRAQ 2D-LC-MS/MS. Compared with DEPs, differentially expressed genes (DEGs) and comprehensive features (CFs), structurally dominant nodes (SDNs) based on integrative topological index distribution produced comparable classification performance in three different clinical settings using five independent gene expression data sets. The signature molecules of SDN-based classifier for distinction of early from late clinical TNM stages were enriched in biological traits of protein synthesis, intracellular localization and ribosome biogenesis, which suggests that ribosome biogenesis represents a promising therapeutic target for treating ESCC. In addition, ITGB1 expression selected exclusively by integrative topological measures correlated with clinical stages and prognosis, which was further validated with two independent cohorts of ESCC samples. Thus the integrative topological analysis of PPI networks proposed in this study provides an alternative approach to identify potential biomarkers and therapeutic targets from MS/MS data with functional insights in ESCC. PMID:26898710

A Roadmap for the Development of Applied Computational Psychiatry.

PubMed

Paulus, Martin P; Huys, Quentin J M; Maia, Tiago V

2016-09-01

Computational psychiatry is a burgeoning field that utilizes mathematical approaches to investigate psychiatric disorders, derive quantitative predictions, and integrate data across multiple levels of description. Computational psychiatry has already led to many new insights into the neurobehavioral mechanisms that underlie several psychiatric disorders, but its usefulness from a clinical standpoint is only now starting to be considered. Examples of computational psychiatry are highlighted, and a phase-based pipeline for the development of clinical computational-psychiatry applications is proposed, similar to the phase-based pipeline used in drug development. It is proposed that each phase has unique endpoints and deliverables, which will be important milestones to move tasks, procedures, computational models, and algorithms from the laboratory to clinical practice. Application of computational approaches should be tested on healthy volunteers in Phase I, transitioned to target populations in Phase IB and Phase IIA, and thoroughly evaluated using randomized clinical trials in Phase IIB and Phase III. Successful completion of these phases should be the basis of determining whether computational models are useful tools for prognosis, diagnosis, or treatment of psychiatric patients. A new type of infrastructure will be necessary to implement the proposed pipeline. This infrastructure should consist of groups of investigators with diverse backgrounds collaborating to make computational psychiatry relevant for the clinic.

How can the cystic fibrosis respiratory microbiome influence our clinical decision-making?

PubMed

Rogers, Geraint B; Bruce, Kenneth D; Hoffman, Lucas R

2017-11-01

Almost 15 years have now passed since bacterial community profiling techniques were first used to analyse respiratory samples from people with cystic fibrosis. Since then, many different analytical approaches have been used to try to better understand the contribution of the cystic fibrosis lung microbiota to disease, with varying degrees of success. We examine the extent to which cystic fibrosis respiratory microbiome research has been successful in informing clinical decision-making, and highlight areas that we believe have the potential to yield important insight. Recent research on the cystic fibrosis lung microbiome can be broadly divided into efforts to better characterize microbiota composition, particularly relative to key clinical events, and attempts to understand the cystic fibrosis lung microbiology as an interactive microbial system. The latter, in particular, has led to the development of a number of models in which microbiome-mediated processes precipitate clinical events. Growing technological sophistication is enabling increasingly detailed microbiological data to be generated from cystic fibrosis respiratory samples. However, translating these data into clinically useful measures that accurately predict outcomes and guide treatments remains a formidable challenge. The development of systems biology approaches that enable the integration of complex microbiome and host-derived data provide an exciting opportunity to address this goal.

Insight in schizophrenia: a review.

PubMed

Dam, Jesper

2006-01-01

The issue of insight in schizophrenia must be assumed to be one of the most important aspects of the clinical examination. Comprehensive studies have shown that between 50% and 80% of all patients suffering from schizophrenia do not believe that they have a disorder. In recent years, poor insight in schizophrenia has been the subject of increasing interest, as manifested in a number of studies discussed in the present review. Some of these studies focus on insight correlated to various parameters such as psychopathology, neuropsychology, clinical relevance and compliance. Other studies refer to more theoretical implications, among these the issue of defining the concept of insight: whether insight can be seen as a "primary" phenomenon in schizophrenia, and whether insight may be graduated, dimensioned or increased. Several authors have developed rating scales in an attempt to obtain a measure for the degree or dimension of insight. Here, the range of parameters employed gives an excellent impression of the complexity of the concept of insight. In the concluding discussion, a phenomenological aspect is brought in, in an attempt to place the concept of insight in relation to disturbances of the self in schizophrenia and to primary symptoms in schizophrenia, amongst these autism.

Bed roughness of palaeo-ice streams: insights and implications for contemporary ice sheet dynamics

NASA Astrophysics Data System (ADS)

Falcini, Francesca; Rippin, David; Selby, Katherine; Krabbendam, Maarten

2017-04-01

Bed roughness is the vertical variation of elevation along a horizontal transect. It is an important control on ice stream location and dynamics, with a correspondingly important role in determining the behaviour of ice sheets. Previous studies of bed roughness have been limited to insights derived from Radio Echo Sounding (RES) profiles across parts of Antarctica and Greenland. Such an approach has been necessary due to the inaccessibility of the underlying bed. This approach has led to important insights, such as identifying a general link between smooth beds and fast ice flow, as well as rough beds and slow ice flow. However, these insights are mainly derived from relatively coarse datasets, so that links between roughness and flow are generalised and rather simplistic. Here, we explore the use of DTMs from the well-preserved footprints of palaeo-ice streams, coupled with high resolution models of palaeo-ice flow, as a tool for investigating basal controls on the behaviour of contemporary, active ice streams in much greater detail. Initially, artificial transects were set up across the Minch palaeo-ice stream (NW Scotland) to mimic RES flight lines from past studies in Antarctica. We then explored how increasing data-resolution impacted upon the roughness measurements that were derived. Our work on the Minch palaeo-ice stream indicates that different roughness signatures are associated with different glacial landforms, and we discuss the potential for using these insights to infer, from RES-based roughness measurements, the occurrence of particular landform assemblages that may exist beneath contemporary ice sheets.

Challenges of assessing critical thinking and clinical judgment in nurse practitioner students.

PubMed

Gorton, Karen L; Hayes, Janice

2014-03-01

The purpose of this study was to determine whether there was a relationship between critical thinking skills and clinical judgment in nurse practitioner students. The study used a convenience, nonprobability sampling technique, engaging participants from across the United States. Correlational analysis demonstrated no statistically significant relationship between critical thinking skills and examination-style questions, critical thinking skills and scores on the evaluation and reevaluation of consequences subscale of the Clinical Decision Making in Nursing Scale, and critical thinking skills and the preceptor evaluation tool. The study found no statistically significant relationships between critical thinking skills and clinical judgment. Educators and practitioners could consider further research in these areas to gain insight into how critical thinking is and could be measured, to gain insight into the clinical decision making skills of nurse practitioner students, and to gain insight into the development and measurement of critical thinking skills in advanced practice educational programs. Copyright 2014, SLACK Incorporated.

Genomics and epigenomics of clear cell renal cell carcinoma: recent developments and potential applications.

PubMed

Rydzanicz, Małgorzata; Wrzesiński, Tomasz; Bluyssen, Hans A R; Wesoły, Joanna

2013-12-01

Majority of clear cell renal cell carcinomas (ccRCCs) are diagnosed in the advanced metastatic stage resulting in dramatic decrease of patient survival. Thereby, early detection and monitoring of the disease may improve prognosis and treatment results. Recent technological advances enable the identification of genetic events associated with ccRCC and reveal significant molecular heterogeneity of ccRCC tumors. This review summarizes recent findings in ccRCC genomics and epigenomics derived from chromosomal aberrations, DNA sequencing and methylation, mRNA, miRNA expression profiling experiments. We provide a molecular insight into ccRCC pathology and recapitulate possible clinical applications of genomic alterations as predictive and prognostic biomarkers. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Effects on cognitive and clinical insight with the use of Guided Self-Determination in outpatients with schizophrenia: A randomized open trial.

PubMed

Jørgensen, R; Licht, R W; Lysaker, P H; Munk-Jørgensen, P; Buck, K D; Jensen, S O W; Hansson, L; Zoffmann, V

2015-07-01

Poor insight has a negative impact on the outcome in schizophrenia; consequently, poor insight is a logical target for treatment. However, neither medication nor psychosocial interventions have been demonstrated to improve poor insight. A method originally designed for diabetes patients to improve their illness management, Guided Self-Determination (GSD), has been adapted for use in patients with schizophrenia (GSD-SZ). The purpose of this study was to investigate the effect on insight of GSD-SZ as a supplement to treatment as usual (TAU) as compared to TAU alone in outpatients diagnosed with schizophrenia. The design was an open randomized trial. The primary hypothesis was cognitive insight would improve in those patients who received GSD-SZ+TAU as assessed by the BCIS. We additionally explored whether the intervention led to changes in clinical insight, self-perceived recovery, self-esteem, social functioning and symptom severity. Assessments were conducted at baseline, and at 3-, 6- and 12-month follow-up. Analysis was based on the principles of intention to treat and potential confounders were taken into account through applying a multivariate approach. A total of 101 participants were randomized to GSD-SZ+TAU (n=50) or to TAU alone (n=51). No statistically significant differences were found on the cognitive insight. However, at 12-month follow-up, clinical insight (measured by G12 from the Positive and Negative Syndrome Scale), symptom severity, and social functioning had statistically significantly improved in the intervention group as compared to the control group. "Improving insight in patients diagnosed with schizophrenia", NCT01282307, http://clinicaltrials.gov/. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Third-person Diagnostic Interview on the Cognitive Insight Level of Psychotic Patients with an Insight at the Denial Level.

PubMed

Mehdizadeh, Mahsa; Rezaei, Omid

2016-01-01

According to the previous findings, the third-person technique improved the clinical insight of psychotic patients, therefore the present study aims to examine the effect of a third-person interview compared to a first-person interview on the level of cognitive insight of psychotic patients with an insight at the denial level. In this study, using interviews and questionnaires, a total number of 44 patients of Razi Psychiatric Educational and Treatment Center with an insight at the denial level being assessed using diagnostic interviews were divided randomly into two groups. Then, the two groups of patients' cognitive insights were evaluated using Beck Cognitive Insight Scale. The findings indicated that in psychotic patients with an insight at the denial level, the third-person technique of interview compared to the first-person had little effect on the improvement of overall cognitive insight and its components, including self-reflection and self-assurance; however, this effect was not strong enough to make a significant difference between the two groups of patients. According to the study findings, we can conclude that the third-person interview compared to the first-person interview has no effect on the improvement of the cognitive insight of psychotic patients with an insight at the denial level. This finding is consistent with the previous studies indicating that although the theory of mind has some correlations with the clinical insight of patients, it has no effect on their cognitive insight.

Insight, social functioning and readmission to hospital in patients with schizophrenia-spectrum disorders: prospective associations.

PubMed

Startup, Mike; Jackson, Mike C; Startup, Sue

2010-06-30

It has been claimed that insight is capable of predicting important clinical outcomes among people with schizophrenia. However, the supporting evidence is sparse. Although many cross-sectional studies have been undertaken, only prospective studies can provide convincing evidence. The aims of the present research were to assess the ability of insight to predict subsequent readmissions to hospital and social functioning. Patients with schizophrenia-spectrum disorders (N=90) were recruited at the time of an acute psychotic episode and then re-assessed after 6, 12, and 24 months. Assessments included insight, three measures of social functioning, and symptoms of psychosis. There was no evidence that having been readmitted to hospital since a previous assessment was associated with insight at the previous assessment. None of the associations between insight at one assessment and social functioning at subsequent assessments was significant. Changes in insight were associated with changes in contemporary functioning, but it was found that changes in insight made no significant contributions to changes in functioning which were independent of changes in symptoms. The general aim of improving clinical outcomes would probably be better met with interventions designed to improve functioning rather than interventions to improve insight.

Cognitive insight: A systematic review.

PubMed

Van Camp, L S C; Sabbe, B G C; Oldenburg, J F E

2017-07-01

Cognitive insight is the ability to re-evaluate thoughts and beliefs in order to make thoughtful conclusions. It differs from clinical insight, as it focuses on more general metacognitive processes. Therefore, it could be relevant to diverse disorders and non-clinical subjects. There is a growing body of research on cognitive insight in individuals with and without psychosis. This review has summarised the current state of the art regarding this topic. We conclude that while cognitive insight in its current form seems valid for use in individuals with psychosis, it is less so for individuals without psychosis. Additionally, higher cognitive insight not always leads to better psychological functioning. For instance, higher levels of self-reflection are often associated with depressive mood. We therefore recommend the sub-components of cognitive insight to be studied separately. Also, it is unclear what position cognitive insight takes within the spectrum of metacognitive processes and how it relates to other self-related concepts that have been defined previously in literature. Combining future and past research on cognitive insight and its analogue concepts will help in the formation of a uniform definition that fits all subjects discussed here. Copyright © 2017. Published by Elsevier Ltd.

Functional magnetic resonance imaging study of external source memory and its relation to cognitive insight in non-clinical subjects.

PubMed

Buchy, Lisa; Hawco, Colin; Bodnar, Michael; Izadi, Sarah; Dell'Elce, Jennifer; Messina, Katrina; Lepage, Martin

2014-09-01

Previous research has linked cognitive insight (a measure of self-reflectiveness and self-certainty) in psychosis with neurocognitive and neuroanatomical disturbances in the fronto-hippocampal neural network. The authors' goal was to use functional magnetic resonance imaging (fMRI) to investigate the neural correlates of cognitive insight during an external source memory paradigm in non-clinical subjects. At encoding, 24 non-clinical subjects travelled through a virtual city where they came across 20 separate people, each paired with a unique object in a distinct location. fMRI data were then acquired while participants viewed images of the city, and completed source recognition memory judgments of where and with whom objects were seen, which is known to involve prefrontal cortex. Cognitive insight was assessed with the Beck Cognitive Insight Scale. External source memory was associated with neural activity in a widespread network consisting of frontal cortex, including ventrolateral prefrontal cortex (VLPFC), temporal and occipital cortices. Activation in VLPFC correlated with higher self-reflectiveness and activation in midbrain correlated with lower self-certainty during source memory attributions. Neither self-reflectiveness nor self-certainty significantly correlated with source memory accuracy. By means of virtual reality and in the context of an external source memory paradigm, the study identified a preliminary functional neural basis for cognitive insight in the VLPFC in healthy people that accords with our fronto-hippocampal theoretical model as well as recent neuroimaging data in people with psychosis. The results may facilitate the understanding of the role of neural mechanisms in psychotic disorders associated with cognitive insight distortions. © 2014 The Authors. Psychiatry and Clinical Neurosciences © 2014 Japanese Society of Psychiatry and Neurology.

The impact of cognitive insight, self-stigma, and medication compliance on the quality of life in patients with schizophrenia.

PubMed

Lien, Yin-Ju; Chang, Hsin-An; Kao, Yu-Chen; Tzeng, Nian-Sheng; Lu, Chien-Wen; Loh, Ching-Hui

2018-02-01

Impaired quality of life (QoL) is a common and clinically relevant feature of schizophrenia. In the present study, we attempted to formulate a model of QoL in the chronic stage of schizophrenia by including key variables-namely cognitive insight, self-stigma, insight into treatment, and medication compliance-that were proposed as its significant predictors in previous studies. We employed structural equation modeling (SEM) to simultaneously test the associations between these variables. A total of 170 community-dwelling patients with schizophrenia participated in this study. Cognitive insight, self-stigma, insight into treatment, medication compliance, and QoL were assessed through self-reporting. Symptoms were rated by interviewers. The influences of cognitive insight, stigma, insight into treatment, and medication compliance on QoL were supported using SEM. Our findings indicated that cognitive insight had a significant, positive, and direct effect on both self-stigma and insight into treatment; in contrast, it had a negative and direct effect on medication compliance. Notably, no evidence indicated a direct effect of cognitive insight on QoL. Thus, individuals with high cognitive insight reported low QoL because of stigma, low medication compliance, and their increased insight into treatment. In contrast, cognitive insight might indirectly ameliorate QoL mediated by the effect of insight into treatment on medication compliance. The findings provide additional support of the links between cognitive and clinical insight, self-stigma, medication compliance, and QoL in those with schizophrenia and suggest the need for screening and intervention services appropriate for this high-risk population.

Insight dimensions in first-episode psychosis patients: clinical, cognitive, pre-morbid and socio-demographic correlates.

PubMed

Ayesa-Arriola, Rosa; Rodríguez-Sánchez, Jose Manuel; Morelli, Chiara; Pelayo-Terán, Jose María; Pérez-Iglesias, Rocío; Mata, Ignacio; Martínez-Garcia, Obdulia; Pardo-Garcia, Gema; Vazquez-Barquero, Jose L; Crespo-Facorro, Benedicto

2011-05-01

To investigate pre-morbid, socio-demographic, clinical and cognitive variables as predictors of insight in a large and representative sample of first-episode psychosis patients. The abbreviated Scale to Assess Unawareness of Mental Disorder was used to assess insight dimensions. Patients with good and poor insight were independently compared on insight dimensions and logistic regression analyses were conducted to identify explanatory variables associated with each insight dimension. The patients with good and poor insight of having a mental disorder differed in duration of untreated psychosis, diagnosis and attention, but only attention appeared as a predictor. The insight of the need for medication groups showed differences in age of onset, depression, severity of disorganized symptoms and hospitalization rate.Nevertheless, age of onset and disorganized symptoms seem to be the predictors. Groups of insight of the social consequences differed in duration of untreated psychosis, the negative and disorganized symptoms severity, disability, education, diagnosis and hospitalization rate.However, exclusively, the severity of disorganized symptoms seems to predict insight of social consequences. When independently analysed, the three insight dimensions showed different rates of affectation and different predictors. These results suggest that there must be different mechanisms underlying the lack of insight. First-episode psychosis is a crucial period for treatment adherence formation, an issue strongly associated with good insight. Thus, a more accurate evaluation of the predictors of lack of insight into each dimension is warranted to achieve a better comprehension of the lack of insight in schizophrenia and in turn, to implement treatment programmes seeking to improve it.

Dimensions of insight in schizophrenia: Exploratory factor analysis of items from multiple self- and interviewer-rated measures of insight.

PubMed

Konsztowicz, Susanna; Schmitz, Norbert; Lepage, Martin

2018-03-10

Insight in schizophrenia is regarded as a multidimensional construct that comprises aspects such as awareness of the disorder and recognition of the need for treatment. The proposed number of underlying dimensions of insight is variable in the literature. In an effort to identify a range of existing dimensions of insight, we conducted a factor analysis on combined items from multiple measures of insight. We recruited 165 participants with enduring schizophrenia (treated for >3years). Exploratory factor analysis was conducted on itemized scores from two interviewer-rated measures of insight: the Schedule for the Assessment of Insight-Expanded and the abbreviated Scale to assess Unawareness of Mental Disorder; and two self-report measures: the Birchwood Insight Scale and the Beck Cognitive Insight Scale. A five-factor solution was selected as the best-fitting model, with the following dimensions of insight: 1) awareness of illness and the need for treatment; 2) awareness and attribution of symptoms and consequences; 3) self-certainty; 4) self-reflectiveness for objectivity and fallibility; and 5) self-reflectiveness for errors in reasoning and openness to feedback. Insight in schizophrenia is a multidimensional construct comprised of distinct clinical and cognitive domains of awareness. Multiple measures of insight, both clinician- and self-rated, are needed to capture all of the existing dimensions of insight. Future exploration of associations between the various dimensions and their potential determinants will facilitate the development of clinically useful models of insight and effective interventions to improve outcome. Copyright © 2018 Elsevier B.V. All rights reserved.

Helminth Infection and Type 1 Diabetes

PubMed Central

Zaccone, Paola; Hall, Samuel W.

2012-01-01

The increasing incidence of type 1 diabetes (T1D) and autoimmune diseases in industrialized countries cannot be exclusively explained by genetic factors. Human epidemiological studies and animal experimental data provide accumulating evidence for the role of environmental factors, such as infections, in the regulation of allergy and autoimmune diseases. The hygiene hypothesis has formally provided a rationale for these observations, suggesting that our co-evolution with pathogens has contributed to the shaping of the present-day human immune system. Therefore, improved sanitation, together with infection control, has removed immunoregulatory mechanisms on which our immune system may depend. Helminths are multicellular organisms that have developed a wide range of strategies to manipulate the host immune system to survive and complete their reproductive cycles successfully. Immunity to helminths involves profound changes in both the innate and adaptive immune compartments, which can have a protective effect in inflammation and autoimmunity. Recently, helminth-derived antigens and molecules have been tested in vitro and in vivo to explore possible applications in the treatment of inflammatory and autoimmune diseases, including T1D. This exciting approach presents numerous challenges that will need to be addressed before it can reach safe clinical application. This review outlines basic insight into the ability of helminths to modulate the onset and progression of T1D, and frames some of the challenges that helminth-derived therapies may face in the context of clinical translation. PMID:23804266

Peptides from the scorpion Vaejovis punctatus with broad antimicrobial activity.

PubMed

Ramírez-Carreto, Santos; Jiménez-Vargas, Juana María; Rivas-Santiago, Bruno; Corzo, Gerardo; Possani, Lourival D; Becerril, Baltazar; Ortiz, Ernesto

2015-11-01

The antimicrobial potential of two new non-disulfide bound peptides, named VpAmp1.0 (LPFFLLSLIPSAISAIKKI, amidated) and VpAmp2.0 (FWGFLGKLAMKAVPSLIGGNKSSSK) is here reported. These are 19- and 25-aminoacid-long peptides with +2 and +4 net charges, respectively. Their sequences correspond to the predicted mature regions from longer precursors, putatively encoded by cDNAs derived from the venom glands of the Mexican scorpion Vaejovis punctatus. Both peptides were chemically synthesized and assayed against a variety of microorganisms, including pathogenic strains from clinical isolates and strains resistant to conventional antibiotics. Two shorter variants, named VpAmp1.1 (FFLLSLIPSAISAIKKI, amidated) and VpAmp2.1 (FWGFLGKLAMKAVPSLIGGNKK), were also synthesized and tested. The antimicrobial assays revealed that the four synthetic peptides effectively inhibit the growth of both Gram-positive (Staphylococcus aureus and Streptococcus agalactiaea) and Gram-negative (Escherichia coli and Pseudomonas aeruginosa) bacteria, with MICs in the range of 2.5-24.0 μM; yeasts (Candida albicans and Candida glabrata) with MICs of 3.1-50.0 μM; and two clinically isolated strains of Mycobacterium tuberculosis-including a multi-drug resistant one- with MICs in the range of 4.8-30.5 μM. A comparison between the activities of the original peptides and their derivatives gives insight into the structural/functional role of their distinctive residues. Copyright © 2015 Elsevier Inc. All rights reserved.

Insight in bipolar mania: evaluation of its heterogeneity and correlation with clinical symptoms.

PubMed

Silva, Rafael de Assis da; Mograbi, Daniel C; Bifano, Jaqueline; Santana, Cristina M T; Cheniaux, Elie

2016-07-15

Studies on insight in bipolar mania are not numerous and usually consider insight as a unitary construct. Evaluate how different facets of insight are affected in bipolar mania and investigate correlations between insight for each specific object in bipolar disorder and manic symptomatology. A group of 165 bipolar patients were followed during a year, with 51 patients having manic episodes according to DSM-IV-TR criteria. Patients underwent a clinical assessment and insight was evaluated through the Insight Scale for Affective Disorders. The study found that insight regarding symptoms is worse than insight of having bipolar disorder, social relationships and self esteem. Moreover, poor global insight (total ISAD) correlates with more severe changes in mood, speech and thought structure, with worse insight about symptoms correlating with the same alterations and also with more severe symptoms of agitation/energy. Although a large sample of bipolar patients was followed up, the final sample composed of patients with at least one manic episode was relatively smaller. Moreover, the fact that the study was performed in a university hospital may have led to selection biases. Results suggest that patients with BD are reasonably capable of identifying that their condition implies consequences but have more impaired awareness of their energy and activity levels. A lower level of insight specifically about symptoms correlates with more severe symptoms of agitation/energy, which suggests a psychomotor nucleus able to impair insight in mania. Copyright © 2016 Elsevier B.V. All rights reserved.

Therapeutic alliance in schizophrenia: the role of recovery orientation, self-stigma, and insight.

PubMed

Kvrgic, Sara; Cavelti, Marialuisa; Beck, Eva-Marina; Rüsch, Nicolas; Vauth, Roland

2013-08-30

The present study examined variables related to the quality of the therapeutic alliance in out-patients with schizophrenia. We expected recovery orientation and insight to be positively, and self-stigma to be negatively associated with a good therapeutic alliance. We expected these associations to be independent from age, clinical symptoms (i.e. positive and negative symptoms, depression), and more general aspects of relationship building like avoidant attachment style and the duration of treatment by the current therapist. The study included 156 participants with DSM-IV diagnoses of schizophrenia or schizoaffective disorder in the maintenance phase of treatment. Therapeutic alliance, recovery orientation, self-stigma, insight, adult attachment style, and depression were assessed by self-report. Symptoms were rated by interviewers. Hierarchical multiple regressions revealed that more recovery orientation, less self-stigma, and more insight independently were associated with a better quality of the therapeutic alliance. Clinical symptoms, adult attachment style, age, and the duration of treatment by current therapist were unrelated to the quality of the therapeutic alliance. Low recovery orientation and increased self-stigma might undermine the therapeutic alliance in schizophrenia beyond the detrimental effect of poor insight. Therefore in clinical settings, besides enhancing insight, recovery orientation, and self-stigma should be addressed. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Instruction-based clinical eye-tracking study on the visual interpretation of divergence: How do students look at vector field plots?

NASA Astrophysics Data System (ADS)

Klein, P.; Viiri, J.; Mozaffari, S.; Dengel, A.; Kuhn, J.

2018-06-01

Relating mathematical concepts to graphical representations is a challenging task for students. In this paper, we introduce two visual strategies to qualitatively interpret the divergence of graphical vector field representations. One strategy is based on the graphical interpretation of partial derivatives, while the other is based on the flux concept. We test the effectiveness of both strategies in an instruction-based eye-tracking study with N =41 physics majors. We found that students' performance improved when both strategies were introduced (74% correct) instead of only one strategy (64% correct), and students performed best when they were free to choose between the two strategies (88% correct). This finding supports the idea of introducing multiple representations of a physical concept to foster student understanding. Relevant eye-tracking measures demonstrate that both strategies imply different visual processing of the vector field plots, therefore reflecting conceptual differences between the strategies. Advanced analysis methods further reveal significant differences in eye movements between the best and worst performing students. For instance, the best students performed predominantly horizontal and vertical saccades, indicating correct interpretation of partial derivatives. They also focused on smaller regions when they balanced positive and negative flux. This mixed-method research leads to new insights into student visual processing of vector field representations, highlights the advantages and limitations of eye-tracking methodologies in this context, and discusses implications for teaching and for future research. The introduction of saccadic direction analysis expands traditional methods, and shows the potential to discover new insights into student understanding and learning difficulties.

Insight among people with severe mental illness, co-occurring PTSD and elevated psychotic symptoms: Correlates and relationship to treatment participation.

PubMed

Yanos, Philip T; Vayshenker, Beth; Pleskach, Pavel; Mueser, Kim T

2016-07-01

There is a dearth of research on what factors are predictive of insight among people with severe mental illness and co-occurring PTSD. Data were drawn from 146 participants with severe mental illness, co-occurring PTSD and elevated psychotic symptoms participating in a randomized controlled trial comparing two interventions for PTSD among people with severe mental illness. We examined the clinical and demographic correlates of insight at baseline, the relationship between baseline insight and treatment participation, the relationship between treatment participation and post-treatment insight, and the relationship between change in insight and change in other clinical variables. Impaired insight was relatively common, with roughly half the sample demonstrating mild or moderate impairment at baseline. Baseline insight was associated with fewer psychotic and disorganized symptoms, and greater emotional discomfort and PTSD knowledge, but was not associated with negative symptoms, PTSD symptoms, depression/anxiety, or treatment participation. Participation in PTSD treatment was associated with increased insight at post-treatment. Improved insight was associated with improvements in disorganization and negative symptoms, but not with knowledge of PTSD or positive symptoms. The findings suggest that engagement in treatment that includes educating people about PTSD may lead to improvements in insight and related improvements in other psychiatric symptoms. Copyright © 2016 Elsevier Inc. All rights reserved.

Chemical insight from density functional modeling of molecular adsorption: Tracking the bonding and diffusion of anthracene derivatives on Cu(111) with molecular orbitals

NASA Astrophysics Data System (ADS)

Wyrick, Jonathan; Einstein, T. L.; Bartels, Ludwig

2015-03-01

We present a method of analyzing the results of density functional modeling of molecular adsorption in terms of an analogue of molecular orbitals. This approach permits intuitive chemical insight into the adsorption process. Applied to a set of anthracene derivates (anthracene, 9,10-anthraquinone, 9,10-dithioanthracene, and 9,10-diselenonanthracene), we follow the electronic states of the molecules that are involved in the bonding process and correlate them to both the molecular adsorption geometry and the species' diffusive behavior. We additionally provide computational code to easily repeat this analysis on any system.

[Lack of insight in schizophrenia: a review. Part I: theoretical concept, clinical aspects and Amador's model].

PubMed

Raffard, S; Bayard, S; Capdevielle, D; Garcia, F; Boulenger, J-P; Gely-Nargeot, M-C

2008-12-01

Schizophrenia is the psychiatric disorder in which the awareness of pathology (or insight) is most frequently altered. A review of the literature shows that between 50 and 80% of patients with schizophrenia do not believe they have a disorder. Studies published on this subject over the two last decades stressed the specificity of this phenomenon in schizophrenic patients, taking into account both its prevalence and its clinical consequences comparatively to other mental disorders. If in bipolar disorders a lack of insight is linked with the intensity and acuteness of symptomatology, there is only a limited relationship between these factors in schizophrenia, thus making lack of insight a trait rather than a state-related symptom. Though defined for a very long time as a dichotomic phenomenon, the recent interest on insight in psychosis and the development of assessment tools for its evaluation have made it possible to underline its multifactorial and dynamic characteristics. Although lack of insight related to pathologies may vary across time in bipolar disorders, the results of clinical studies suggest that this phenomenon remains stable in schizophrenia. CONCEPTUAL PROPOSALS: In this review, we will reconsider the evolution of this concept in psychiatry and its definition. The clinical characteristics, which are specifically associated with the lack of insight in schizophrenia will be outlined. We will describe more specifically the model of Amador and Strauss and their assessment tool: the Scale to Assess Unawareness of Mental Disorder (SUMD). This model developed since the 1990s takes into account the time-related evolution of insight, and can be applied both to bipolar and psychotic disorders. The SUMD has six general items and four subscales. The general items estimate the three most widely used definitions of insight: awareness of having a mental disorder, awareness of the achieved effects of medication and awareness of the social consequences of having a mental disorder, and include assessment of both current and past-time periods. Four other subscales, each composed of 17 items, assess awareness and attribution of specific current and retrospective symptoms as well as deficits associated with severe mental disorders. Insight, thus, appears as a multidimensional and continuous phenomenon, since patients' awareness may apply only to part of their symptoms and vary over time. In this article, we will review existing scales assessing insight in schizophrenia. The deficiency of available scales validated in French limits the number of scientific publications concerning this important aspect of the clinical evaluation of schizophrenic patients. THERAPEUTICAL ASPECTS: Finally, interventions to improve insight in patients with schizophrenia are presented. Recent studies have shown cognitive behavioural therapy (CBT) to be of benefit in the treatment of poor insight in schizophrenia. Evidence suggests that early diagnosis and treatment of schizophrenia leads to better prognosis. An important suggestion from theses studies may be that psychosocial therapy needs to focus on explanations that are in tune with the culture, rather than focus on diagnostic labels.

Large-Scale Wearable Sensor Deployment in Parkinson’s Patients: The Parkinson@Home Study Protocol

PubMed Central

Hahn, Tim; de Vries, Nienke M; Cohen, Eli; Bataille, Lauren; Little, Max A; Baldus, Heribert; Bloem, Bastiaan R; Faber, Marjan J

2016-01-01

Background Long-term management of Parkinson’s disease does not reach its full potential because we lack knowledge about individual variations in clinical presentation and disease progression. Continuous and longitudinal assessments in real-life (ie, within the patients’ own home environment) might fill this knowledge gap. Objective The primary aim of the Parkinson@Home study is to evaluate the feasibility and compliance of using multiple wearable sensors to collect clinically relevant data. Our second aim is to address the usability of these data for answering clinical research questions. Finally, we aim to build a database for future validation of novel algorithms applied to sensor-derived data from Parkinson’s patients during daily functioning. Methods The Parkinson@Home study is a two-phase observational study involving 1000 Parkinson’s patients and 250 physiotherapists. Disease status is assessed using a short version of the Parkinson's Progression Markers Initiative protocol, performed by certified physiotherapists. Additionally, participants will wear a set of sensors (smartwatch, smartphone, and fall detector), and use these together with a customized smartphone app (Fox Insight), 24/7 for 3 months. The sensors embedded within the smartwatch and fall detector may be used to estimate physical activity, tremor, sleep quality, and falls. Medication intake and fall incidents will be measured via patients’ self-reports in the smartphone app. Phase one will address the feasibility of the study protocol. In phase two, mathematicians will distill relevant summary statistics from the raw sensor signals, which will be compared against the clinical outcomes. Results Recruitment of 300 participants for phase one was concluded in March, 2016, and the follow-up period will end in June, 2016. Phase two will include the remaining participants, and will commence in September, 2016. Conclusions The Parkinson@Home study is expected to generate new insights into the feasibility of integrating self-collected information from wearable sensors into both daily routines and clinical practices for Parkinson’s patients. This study represents an important step towards building a reliable system that translates and integrates real-life information into clinical decisions, with the long-term aim of delivering personalized disease management support. ClinicalTrial ClinicalTrials.gov NCT02474329; https://clinicaltrials.gov/ct2/show/NCT02474329 (Archived at http://www.webcitation.org/6joEc5P1v) PMID:27565186

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhao, T; Ruan, D

Purpose: The growing size and heterogeneity in training atlas necessitates sophisticated schemes to identify only the most relevant atlases for the specific multi-atlas-based image segmentation problem. This study aims to develop a model to infer the inaccessible oracle geometric relevance metric from surrogate image similarity metrics, and based on such model, provide guidance to atlas selection in multi-atlas-based image segmentation. Methods: We relate the oracle geometric relevance metric in label space to the surrogate metric in image space, by a monotonically non-decreasing function with additive random perturbations. Subsequently, a surrogate’s ability to prognosticate the oracle order for atlas subset selectionmore » is quantified probabilistically. Finally, important insights and guidance are provided for the design of fusion set size, balancing the competing demands to include the most relevant atlases and to exclude the most irrelevant ones. A systematic solution is derived based on an optimization framework. Model verification and performance assessment is performed based on clinical prostate MR images. Results: The proposed surrogate model was exemplified by a linear map with normally distributed perturbation, and verified with several commonly-used surrogates, including MSD, NCC and (N)MI. The derived behaviors of different surrogates in atlas selection and their corresponding performance in ultimate label estimate were validated. The performance of NCC and (N)MI was similarly superior to MSD, with a 10% higher atlas selection probability and a segmentation performance increase in DSC by 0.10 with the first and third quartiles of (0.83, 0.89), compared to (0.81, 0.89). The derived optimal fusion set size, valued at 7/8/8/7 for MSD/NCC/MI/NMI, agreed well with the appropriate range [4, 9] from empirical observation. Conclusion: This work has developed an efficacious probabilistic model to characterize the image-based surrogate metric on atlas selection. Analytical insights lead to valid guiding principles on fusion set size design.« less

Ethanol and liver: Recent insights into the mechanisms of ethanol-induced fatty liver

PubMed Central

Liu, Jinyao

2014-01-01

Alcoholic fatty liver disease (AFLD), a potentially pathologic condition, can progress to steatohepatitis, fibrosis, and cirrhosis, leading to an increased probability of hepatic failure and death. Alcohol induces fatty liver by increasing the ratio of reduced form of nicotinamide adenine dinucleotide to oxidized form of nicotinamide adenine dinucleotide in hepatocytes; increasing hepatic sterol regulatory element-binding protein (SREBP)-1, plasminogen activator inhibitor (PAI)-1, and early growth response-1 activity; and decreasing hepatic peroxisome proliferator-activated receptor-α activity. Alcohol activates the innate immune system and induces an imbalance of the immune response, which is followed by activated Kupffer cell-derived tumor necrosis factor (TNF)-α overproduction, which is in turn responsible for the changes in the hepatic SREBP-1 and PAI-1 activity. Alcohol abuse promotes the migration of bone marrow-derived cells (BMDCs) to the liver and then reprograms TNF-α expression from BMDCs. Chronic alcohol intake triggers the sympathetic hyperactivity-activated hepatic stellate cell (HSC) feedback loop that in turn activates the HSCs, resulting in HSC-derived TNF-α overproduction. Carvedilol may block this feedback loop by suppressing sympathetic activity, which attenuates the progression of AFLD. Clinical studies evaluating combination therapy of carvedilol with a TNF-α inhibitor to treat patients with AFLD are warranted to prevent the development of alcoholic liver disease. PMID:25356030

The relationship between insight and the level of expressed emotion in patients with obsessive-compulsive disorder.

PubMed

Ozkiris, Ayse; Essizoglu, Altan; Gulec, Gulcan; Aksaray, Gokay

2015-04-01

The aim of this study is firstly to compare the obsessive-compulsive disorder (OCD) patients with good insight and OCD patients with poor insight in terms of socio-demographic and clinical features; to investigate the relation between insight and the level of the expressed emotion (EE) in the patients; and lastly to specify the factors that predict level of insight. OCD patients with good insight and patients with poor insight were compared in terms of clinical features and the perceived EE level of the patients and the individuals that they live with in order to specify the factors that predict the insight level, and to investigate the relationship between insight level and EE. It was found that the total Expressed Emotion Scale, total Level of Expressed Emotion (LEE), LEE-Emotional Response and LEE-Tolerance/Expectation subscale scores of the group comprised of patients with poor insight are higher than the other group. The results also show that the duration of illness and Yale-Brown Obsessive Compulsive Scale (Y-BOCS) total score predict insight level. This study shows that the level of EE perceived by the patients with poor insight and the person that he/she lives with, is higher than the group with good insight. The studies that investigate the relationship between the factors of insight level and EE level, which are indicated to determine the level of the illness severity and its chronicity, will enable the researchers to understand the importance of the role of the family on the treatment processes of OCD.

Neurobiological Basis of Insight in Schizophrenia: A Systematic Review.

PubMed

Xavier, Rose Mary; Vorderstrasse, Allison

2016-01-01

Insight in schizophrenia is defined as awareness into illness, symptoms, and need for treatment and has long been associated with cognition, other psychopathological symptoms, and several adverse clinical and functional outcomes. However, the biological basis of insight is not clearly understood. The aim of this systematic review was to critically evaluate and summarize advances in the study of the biological basis of insight in schizophrenia and to identify gaps in this knowledge. A literature search of PubMed, CINAHL, PsycINFO, and EMBASE databases was conducted using search terms to identify articles relevant to the biology of insight in schizophrenia published in the last 6 years. Articles that focused on etiology of insight in schizophrenia and those that examined the neurobiology of insight in schizophrenia or psychoses were chosen for analysis. Articles on insight in conditions other than schizophrenia or psychoses and which did not investigate the neurobiological underpinnings of insight were excluded from the review. Twenty-six articles met the inclusion criteria for this review. Of the 26 articles, 3 focused on cellular abnormalities and 23 were neuroimaging studies. Preliminary data identify the prefrontal cortex, cingulate cortex, and regions of the temporal and parietal lobe (precuneus, inferior parietal lobule) and hippocampus as the neural correlates of insight. A growing body of literature attests to the neurobiological basis of insight in schizophrenia. Current evidence supports the neurobiological basis of insight in schizophrenia and identifies specific neural correlates for insight types and its dimensions. Further studies that examine the precise biological mechanisms of insight are needed to apply this knowledge to effective clinical intervention development.

Third-person Diagnostic Interview on the Cognitive Insight Level of Psychotic Patients with an Insight at the Denial Level

PubMed Central

Mehdizadeh, Mahsa; Rezaei, Omid

2016-01-01

Objectives: According to the previous findings, the third-person technique improved the clinical insight of psychotic patients, therefore the present study aims to examine the effect of a third-person interview compared to a first-person interview on the level of cognitive insight of psychotic patients with an insight at the denial level. Materials and Methods: In this study, using interviews and questionnaires, a total number of 44 patients of Razi Psychiatric Educational and Treatment Center with an insight at the denial level being assessed using diagnostic interviews were divided randomly into two groups. Then, the two groups of patients' cognitive insights were evaluated using Beck Cognitive Insight Scale. Results: The findings indicated that in psychotic patients with an insight at the denial level, the third-person technique of interview compared to the first-person had little effect on the improvement of overall cognitive insight and its components, including self-reflection and self-assurance; however, this effect was not strong enough to make a significant difference between the two groups of patients. Conclusion: According to the study findings, we can conclude that the third-person interview compared to the first-person interview has no effect on the improvement of the cognitive insight of psychotic patients with an insight at the denial level. This finding is consistent with the previous studies indicating that although the theory of mind has some correlations with the clinical insight of patients, it has no effect on their cognitive insight. PMID:27335517

Insights from clinical research completed during the west Africa Ebola virus disease epidemic

PubMed Central

Rojek, Amanda; Horby, Peter; Dunning, Jake

2018-01-01

The west Africa Ebola virus disease (EVD) epidemic was extraordinary in scale. Now that the epidemic has ended, it is a relevant time to examine published studies with direct relevance to clinical care and, more broadly, to examine the implications of the clinical research response mounted. Clinically relevant research includes literature detailing risk factors for and clinical manifestations of EVD, laboratory and other investigation findings in patients, experimental vaccine and therapeutic clinical trials, and analyses of survivor syndrome. In this Review, we discuss new insights from patient-oriented research completed during the west Africa epidemic, identify ongoing knowledge gaps, and suggest priorities for future research. PMID:28461209

Relational Network for Knowledge Discovery through Heterogeneous Biomedical and Clinical Features

PubMed Central

Chen, Huaidong; Chen, Wei; Liu, Chenglin; Zhang, Le; Su, Jing; Zhou, Xiaobo

2016-01-01

Biomedical big data, as a whole, covers numerous features, while each dataset specifically delineates part of them. “Full feature spectrum” knowledge discovery across heterogeneous data sources remains a major challenge. We developed a method called bootstrapping for unified feature association measurement (BUFAM) for pairwise association analysis, and relational dependency network (RDN) modeling for global module detection on features across breast cancer cohorts. Discovered knowledge was cross-validated using data from Wake Forest Baptist Medical Center’s electronic medical records and annotated with BioCarta signaling signatures. The clinical potential of the discovered modules was exhibited by stratifying patients for drug responses. A series of discovered associations provided new insights into breast cancer, such as the effects of patient’s cultural background on preferences for surgical procedure. We also discovered two groups of highly associated features, the HER2 and the ER modules, each of which described how phenotypes were associated with molecular signatures, diagnostic features, and clinical decisions. The discovered “ER module”, which was dominated by cancer immunity, was used as an example for patient stratification and prediction of drug responses to tamoxifen and chemotherapy. BUFAM-derived RDN modeling demonstrated unique ability to discover clinically meaningful and actionable knowledge across highly heterogeneous biomedical big data sets. PMID:27427091

Relational Network for Knowledge Discovery through Heterogeneous Biomedical and Clinical Features

NASA Astrophysics Data System (ADS)

Chen, Huaidong; Chen, Wei; Liu, Chenglin; Zhang, Le; Su, Jing; Zhou, Xiaobo

2016-07-01

Biomedical big data, as a whole, covers numerous features, while each dataset specifically delineates part of them. “Full feature spectrum” knowledge discovery across heterogeneous data sources remains a major challenge. We developed a method called bootstrapping for unified feature association measurement (BUFAM) for pairwise association analysis, and relational dependency network (RDN) modeling for global module detection on features across breast cancer cohorts. Discovered knowledge was cross-validated using data from Wake Forest Baptist Medical Center’s electronic medical records and annotated with BioCarta signaling signatures. The clinical potential of the discovered modules was exhibited by stratifying patients for drug responses. A series of discovered associations provided new insights into breast cancer, such as the effects of patient’s cultural background on preferences for surgical procedure. We also discovered two groups of highly associated features, the HER2 and the ER modules, each of which described how phenotypes were associated with molecular signatures, diagnostic features, and clinical decisions. The discovered “ER module”, which was dominated by cancer immunity, was used as an example for patient stratification and prediction of drug responses to tamoxifen and chemotherapy. BUFAM-derived RDN modeling demonstrated unique ability to discover clinically meaningful and actionable knowledge across highly heterogeneous biomedical big data sets.

Identifying Exosome-Derived MicroRNAs as Candidate Biomarkers of Frailty.

PubMed

Ipson, B R; Fletcher, M B; Espinoza, S E; Fisher, A L

2018-01-01

Frailty is a geriatric syndrome associated with progressive physical decline and significantly increases risk for falls, disability, hospitalizations, and death. However, much remains unknown regarding the biological mechanisms that contribute to aging and frailty, and to date, there are no clinically used prognostic or diagnostic molecular biomarkers. The present study profiled exosome-derived microRNAs isolated from the plasma of young, robust older, and frail older individuals and identified eight miRNAs that are uniquely enriched in frailty: miR-10a-3p, miR-92a-3p, miR-185-3p, miR-194-5p, miR-326, miR-532-5p, miR-576-5p, and miR-760. Furthermore, since exosomes can deliver miRNAs to alter cellular activity and behavior, these miRNAs may also provide insights into the biological mechanisms underlying frailty; KEGG analysis of their target genes revealed multiple pathways implicated in aging and age-related processes. Although further validation and research studies are warranted, our study identified eight novel candidate biomarkers of frailty that may help to elucidate the multifactorial pathogenesis of frailty.

C-2 (E)-4-(Styryl)aniline substituted diphenylpyrimidine derivatives (Sty-DPPYs) as specific kinase inhibitors targeting clinical resistance related EGFRT790M mutant.

PubMed

Song, Anran; Zhang, Jianbin; Ge, Yang; Wang, Changyuan; Meng, Qiang; Tang, Zeyao; Peng, Jinyong; Liu, Kexin; Li, Yanxia; Ma, Xiaodong

2017-05-15

With the aim to overcome the drug resistance induced by the EGFR T790M mutation (EGFR T790M ), herein, a family of diphenylpyrimidine derivatives (Sty-DPPYs) bearing a C-2 (E)-4-(styryl)aniline functionality were designed and synthesized as potential EGFR T790M inhibitors. Among them, the compound 10e displayed strong potency against the EGFR T790M enzyme, with the IC 50 of 11.0nM. Compound 10e also showed a higher SI value (SI=49.0) than rociletinib (SI=21.4), indicating its less side effect. In addition, compound 10e could effectively inhibit the proliferation of H1975 cells harboring the EGFR T790M mutation, within the concentration of 2.91μM. Significantly, compound 10e has low toxicity against the normal HBE cell (IC 50 =22.48μM). This work provided new insights into the discovery of potent and selective inhibitor against EGFR T790M over wild-type (EGFR WT ). Copyright © 2017 Elsevier Ltd. All rights reserved.

Integrating Dynamic Positron Emission Tomography and Conventional Pharmacokinetic Studies to Delineate Plasma and Tumor Pharmacokinetics of FAU, a Prodrug Bioactivated by Thymidylate Synthase.

PubMed

Li, Jing; Kim, Seongho; Shields, Anthony F; Douglas, Kirk A; McHugh, Christopher I; Lawhorn-Crews, Jawana M; Wu, Jianmei; Mangner, Thomas J; LoRusso, Patricia M

2016-11-01

FAU, a pyrimidine nucleotide analogue, is a prodrug bioactivated by intracellular thymidylate synthase to form FMAU, which is incorporated into DNA, causing cell death. This study presents a model-based approach to integrating dynamic positron emission tomography (PET) and conventional plasma pharmacokinetic studies to characterize the plasma and tissue pharmacokinetics of FAU and FMAU. Twelve cancer patients were enrolled into a phase 1 study, where conventional plasma pharmacokinetic evaluation of therapeutic FAU (50-1600 mg/m 2 ) and dynamic PET assessment of 18 F-FAU were performed. A parent-metabolite population pharmacokinetic model was developed to simultaneously fit PET-derived tissue data and conventional plasma pharmacokinetic data. The developed model enabled separation of PET-derived total tissue concentrations into the parent drug and metabolite components. The model provides quantitative, mechanistic insights into the bioactivation of FAU and retention of FMAU in normal and tumor tissues and has potential utility to predict tumor responsiveness to FAU treatment. © 2016, The American College of Clinical Pharmacology.

Liquid chromatography/mass spectrometry-based plasma metabolic profiling study of escitalopram in subjects with major depressive disorder.

PubMed

Bandu, Raju; Lee, Hyun Jeong; Lee, Hyeong Min; Ha, Tae Hyon; Lee, Heon-Jeong; Kim, Se Joo; Ha, Kyooseob; Kim, Kwang Pyo

2018-05-01

Liquid chromatography-mass spectrometry (LC-MS) method revealed the plasma metabolite profiles in major depressive disorder patients treated with escitalopram (ECTP) (n = 7). Depression severity was assessed according to the 17-item Hamilton Depression Rating Scale. Metabolic profiles were derived from major depressive disorder subject blood samples collected after ECTP treatment. Blood plasma was separated and processed in order to effectively extract metabolites, which were then analyzed using LC-MS. We identified 19 metabolites and elucidated their structures using LC-tandem MS (LC-MS/MS) combined with elemental compositions derived from accurate mass measurements. We further used online H/D exchange experiments to verify the structural elucidations of each metabolite. Identifying molecular metabolites may provide critical insights into the pharmacological and clinical effects of ECTP treatment and may also provide useful information informing the development of new antidepressant treatments. These detailed plasma metabolite analyses may also be used to identify optimal dose concentrations in psychopharmacotherapeutic treatment through drug monitoring, as well as forming the basis for response predictions in depressed subjects. Copyright © 2018 John Wiley & Sons, Ltd.

Absence of Ret Signaling in Mice Causes Progressive and Late Degeneration of the Nigrostriatal System

PubMed Central

Kramer, Edgar R; Aron, Liviu; Ramakers, Geert M. J; Seitz, Sabine; Zhuang, Xiaoxi; Beyer, Klaus; Smidt, Marten P; Klein, Rüdiger

2007-01-01

Support of ageing neurons by endogenous neurotrophic factors such as glial cell line–derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF) may determine whether the neurons resist or succumb to neurodegeneration. GDNF has been tested in clinical trials for the treatment of Parkinson disease (PD), a common neurodegenerative disorder characterized by the loss of midbrain dopaminergic (DA) neurons. BDNF modulates nigrostriatal functions and rescues DA neurons in PD animal models. The physiological roles of GDNF and BDNF signaling in the adult nigrostriatal DA system are unknown. We generated mice with regionally selective ablations of the genes encoding the receptors for GDNF (Ret) and BDNF (TrkB). We find that Ret, but not TrkB, ablation causes progressive and adult-onset loss of DA neurons specifically in the substantia nigra pars compacta, degeneration of DA nerve terminals in striatum, and pronounced glial activation. These findings establish Ret as a critical regulator of long-term maintenance of the nigrostriatal DA system and suggest conditional Ret mutants as useful tools for gaining insights into the molecular mechanisms involved in the development of PD. PMID:17298183

Snake venom: From fieldwork to the clinic: Recent insights into snake biology, together with new technology allowing high-throughput screening of venom, bring new hope for drug discovery.

PubMed

Vonk, Freek J; Jackson, Kate; Doley, Robin; Madaras, Frank; Mirtschin, Peter J; Vidal, Nicolas

2011-04-01

Snake venoms are recognized here as a grossly under-explored resource in pharmacological prospecting. Discoveries in snake systematics demonstrate that former taxonomic bias in research has led to the neglect of thousands of species of potential medical use. Recent discoveries reveal an unexpectedly vast degree of variation in venom composition among snakes, from different species down to litter mates. The molecular mechanisms underlying this diversity are only beginning to be understood. However, the enormous potential that this resource represents for pharmacological prospecting is clear. New high-throughput screening systems offer greatly increased speed and efficiency in identifying and extracting therapeutically useful molecules. At the same time a global biodiversity crisis is threatening the very snake populations on which hopes for new venom-derived medications depend. Biomedical researchers, pharmacologists, clinicians, herpetologists, and conservation biologists must combine their efforts if the full potential of snake venom-derived medications is to be realized. Copyright © 2011 WILEY Periodicals, Inc.

An Exploratory Study of Student Engagement at Transnational Education Initiatives: Proactive or Apathetic?

ERIC Educational Resources Information Center

Maxwell-Stuart, Rebecca; Huisman, Jeroen

2018-01-01

Purpose: Although there is increasing insight in student engagement (SE) in higher education, there is limited insight in how students experience SE in a transnational setting. The purpose of this paper is to explore SE perceptions and transnational experiences. A model, derived from the literature, representing four student identities (consumer,…

[Lack of insight in schizophrenia: a review].

PubMed

Raffard, S; Bayard, S; Capdevielle, D; Garcia, F; Boulenger, J-P; Gely-Nargeot, M-C

2008-10-01

Relative to other psychiatric disorders, patients with schizophrenia are often unaware of the consequences of their disease and their need for treatment. These deficits in awareness referred in general in the English literature as "poor insight", have been the focus of many clinical studies over recent years. This phenomenon, which is considered as fundamental in clinical evaluations of schizophrenia, should be understood as a multidimensional process rather than a dichotomic phenomenon, as is presently the case. The links between insight deficits and responses to vocational rehabilitation efforts represent a major interest in research, including those related to medication compliance and clinical outcome. To conduct such studies, various evaluation tools have been developed, enabling the assessment of insight, of its time-course and of its components in psychosis and schizophrenia spectrum disorders. The Scale to Assess Unawareness of illness in Mental Disorders (SUMD) developed by Amador and Strauss appears to be the most frequently used scale for the evaluation of awareness of the disorder in schizophrenia. Although the model proposed by Amador and Strauss is considered as the privileged model in the multidimensional approach of insight, it corresponds only to a phenomenological analysis of this concept. In the second part of this article, we thus review the current models attempting to explain the lack of insight in schizophrenia. Four current explanatory models of lack of insight will be described as follows: resulting either from adaptation or defence mechanisms to environmental stressors, resulting from cognitive bias of data processing, resulting from neuropsychological functional deficits and resulting from metacognitive deficits. Several hypotheses concerning these deficits arise from clinical studies. Although coping, and defence mechanisms to the consequences and stigmatization of the disease were hardly studied, the fact that poor insight does not appear related to the severity of symptomatology or to the emotional state of the patients argue against this hypothesis. Conversely, a considerable body of literature emphasized how unawareness may result from cognitive deficits. Research in neuropsychology and cognitive psychology has provided consistent results concerning the link between deficit in executive functions, frontal lobe dysfunction and poor insight. Recent studies on bias in cognitive information treatment and social cognition theories currently open new prospects.

Bone Repair Cells for Craniofacial Regeneration

PubMed Central

Pagni, G; Kaigler, D; Rasperini, G; Avila-Ortiz, G; Bartel, R; Giannobile, WV

2012-01-01

Reconstruction of complex craniofacial deformities is a clinical challenge in situations of injury, congenital defects or disease. The use of cell-based therapies represents one of the most advanced methods for enhancing the regenerative response for craniofacial wound healing. Both Somatic and Stem Cells have been adopted in the treatment of complex osseous defects and advances have been made in finding the most adequate scaffold for the delivery of cell therapies in human regenerative medicine. As an example of such approaches for clinical application for craniofacial regeneration, Ixmyelocel-T or bone repair cells are a source of bone marrow derived stem and progenitor cells. They are produced through the use of single pass perfusion bioreactors for CD90+ mesenchymal stem cells and CD14+ monocyte/macrophage progenitor cells. The application of ixmyelocel-T has shown potential in the regeneration of muscular, vascular, nervous and osseous tissue. The purpose of this manuscript is to highlight cell therapies used to repair bony and soft tissue defects in the oral and craniofacial complex. The field at this point remains at an early stage, however this review will provide insights into the progress being made using cell therapies for eventual development into clinical practice. PMID:22433781

Mathematical Modelling of the Infusion Test

NASA Astrophysics Data System (ADS)

Cieslicki, Krzysztof

2007-01-01

The objective of this paper was to improve the well established in clinical practice Marmarou model for intracranial volume-pressure compensation by adding the pulsatile components. It was demonstrated that complicated pulsation and growth in intracranial pressure during infusion test could be successfully modeled by the relatively simple analytical expression derived in this paper. The CSF dynamics were tested in 25 patients with clinical symptoms of hydrocephalus. Basing on the frequency spectrum of the patient's baseline pressure and identified parameters of CSF dynamic, for each patient an "ideal" infusion test curve free from artefacts and slow waves was simulated. The degree of correlation between simulated and real curves obtained from clinical observations gave insight into the adequacy of assumptions of Marmarou model. The proposed method of infusion tests analysis designates more exactly the value of the reference pressure, which is usually treated as a secondary and of uncertain significance. The properly identified value of the reference pressure decides on the degree of pulsation amplitude growth during IT, as well as on the value of elastance coefficient. The artificially generated tests with various pulsation components were also applied to examine the correctness of the used algorithm of identification of the original Marmarou model parameters.

Social Networking Sites and Addiction: Ten Lessons Learned

PubMed Central

Kuss, Daria J.; Griffiths, Mark D.

2017-01-01

Online social networking sites (SNSs) have gained increasing popularity in the last decade, with individuals engaging in SNSs to connect with others who share similar interests. The perceived need to be online may result in compulsive use of SNSs, which in extreme cases may result in symptoms and consequences traditionally associated with substance-related addictions. In order to present new insights into online social networking and addiction, in this paper, 10 lessons learned concerning online social networking sites and addiction based on the insights derived from recent empirical research will be presented. These are: (i) social networking and social media use are not the same; (ii) social networking is eclectic; (iii) social networking is a way of being; (iv) individuals can become addicted to using social networking sites; (v) Facebook addiction is only one example of SNS addiction; (vi) fear of missing out (FOMO) may be part of SNS addiction; (vii) smartphone addiction may be part of SNS addiction; (viii) nomophobia may be part of SNS addiction; (ix) there are sociodemographic differences in SNS addiction; and (x) there are methodological problems with research to date. These are discussed in turn. Recommendations for research and clinical applications are provided. PMID:28304359

Social Networking Sites and Addiction: Ten Lessons Learned.

PubMed

Kuss, Daria J; Griffiths, Mark D

2017-03-17

Online social networking sites (SNSs) have gained increasing popularity in the last decade, with individuals engaging in SNSs to connect with others who share similar interests. The perceived need to be online may result in compulsive use of SNSs, which in extreme cases may result in symptoms and consequences traditionally associated with substance-related addictions. In order to present new insights into online social networking and addiction, in this paper, 10 lessons learned concerning online social networking sites and addiction based on the insights derived from recent empirical research will be presented. These are: (i) social networking and social media use are not the same; (ii) social networking is eclectic; (iii) social networking is a way of being; (iv) individuals can become addicted to using social networking sites; (v) Facebook addiction is only one example of SNS addiction; (vi) fear of missing out (FOMO) may be part of SNS addiction; (vii) smartphone addiction may be part of SNS addiction; (viii) nomophobia may be part of SNS addiction; (ix) there are sociodemographic differences in SNS addiction; and (x) there are methodological problems with research to date. These are discussed in turn. Recommendations for research and clinical applications are provided.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu, Zhe; Wu, Chaochao; Xie, Fang

Aberrant degradation of proteins is associated with many pathological states, including cancers. Mass spectrometric analysis of tumor peptidomes, the intracellular and intercellular products of protein degradation, has the potential to provide biological insights on proteolytic processing in cancer. However, attempts to use the information on these smaller protein degradation products from tumors for biomarker discovery and cancer biology studies have been fairly limited to date, largely due to the lack of effective approaches for robust peptidomics identification and quantification, and the prevalence of confounding factors and biases associated with sample handling and processing. Herein, we have developed an effective andmore » robust analytical platform for comprehensive analyses of tissue peptidomes, which is suitable for high throughput quantitative studies. The reproducibility and coverage of the platform, as well as the suitability of clinical ovarian tumor and patient-derived breast tumor xenograft samples with post-excision delay of up to 60 min before freezing for peptidomics analysis, have been demonstrated. Moreover, our data also show that the peptidomics profiles can effectively separate breast cancer subtypes, reflecting tumor-associated protease activities. Peptidomics complements results obtainable from conventional bottom-up proteomics, and provides insights not readily obtainable from such approaches.« less

Comprehensive Quantitative Analysis of Ovarian and Breast Cancer Tumor Peptidomes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Xu, Zhe; Wu, Chaochao; Xie, Fang

Aberrant degradation of proteins is associated with many pathological states, including cancers. Mass spectrometric analysis of tumor peptidomes, the intracellular and intercellular products of protein degradation, has the potential to provide biological insights on proteolytic processing in cancer. However, attempts to use the information on these smaller protein degradation products from tumors for biomarker discovery and cancer biology studies have been fairly limited to date, largely due to the lack of effective approaches for robust peptidomics identification and quantification, and the prevalence of confounding factors and biases associated with sample handling and processing. Herein, we have developed an effective andmore » robust analytical platform for comprehensive analyses of tissue peptidomes, and which is suitable for high throughput quantitative studies. The reproducibility and coverage of the platform, as well as the suitability of clinical ovarian tumor and patient-derived breast tumor xenograft samples with post-excision delay of up to 60 min before freezing for peptidomics analysis, have been demonstrated. Additionally, our data also show that the peptidomics profiles can effectively separate breast cancer subtypes, reflecting tumor-associated protease activities. In conclusion, peptidomics complements results obtainable from conventional bottom-up proteomics, and provides insights not readily obtainable from such approaches.« less

Comprehensive Quantitative Analysis of Ovarian and Breast Cancer Tumor Peptidomes

DOE PAGES

Xu, Zhe; Wu, Chaochao; Xie, Fang; ...

2014-10-28

Aberrant degradation of proteins is associated with many pathological states, including cancers. Mass spectrometric analysis of tumor peptidomes, the intracellular and intercellular products of protein degradation, has the potential to provide biological insights on proteolytic processing in cancer. However, attempts to use the information on these smaller protein degradation products from tumors for biomarker discovery and cancer biology studies have been fairly limited to date, largely due to the lack of effective approaches for robust peptidomics identification and quantification, and the prevalence of confounding factors and biases associated with sample handling and processing. Herein, we have developed an effective andmore » robust analytical platform for comprehensive analyses of tissue peptidomes, and which is suitable for high throughput quantitative studies. The reproducibility and coverage of the platform, as well as the suitability of clinical ovarian tumor and patient-derived breast tumor xenograft samples with post-excision delay of up to 60 min before freezing for peptidomics analysis, have been demonstrated. Additionally, our data also show that the peptidomics profiles can effectively separate breast cancer subtypes, reflecting tumor-associated protease activities. In conclusion, peptidomics complements results obtainable from conventional bottom-up proteomics, and provides insights not readily obtainable from such approaches.« less

The assessment of insight in psychosis.

PubMed

David, A; Buchanan, A; Reed, A; Almeida, O

1992-11-01

An assessment schedule was used to determine the nature of insight in 91 mixed psychotic patients, and to examine its distribution and associations. While all the components of the schedule intercorrelated significantly, scores for compliance were only weakly related to those for ability to label psychotic phenomena as abnormal. Compliance and illness recognition were related to IQ. Total insight score was inversely correlated, moderately, with a global measure of psychopathology derived from the PSE, and was less in patients involuntarily committed. Age, sex, diagnosis, and the number of previous hospital admissions had little effect. The results support the notion that insight is not a unitary concept.

A cross-sectional study of insight and family accommodation in pediatric obsessive-compulsive disorder

PubMed Central

2013-01-01

Background Factors predicting treatment outcome in pediatric patients with obsessive-compulsive disorder (OCD) include disease severity, functional impairment, comorbid disorders, insight, and family accommodation (FA). Treatment of pediatric OCD is often only partly successful as some of these predictors are not targeted with conventional therapy. Among these, insight and FA were identified to be modifiable predictors of special relevance to pediatric OCD. Despite their clinical relevance, insight and FA remain understudied in youth with OCD. This study examined the clinical correlates of insight and FA and determined whether FA mediates the relationship between symptom severity and functional impairment in pediatric OCD. Methods This was a cross-sectional, outpatient study. Thirty-five treatment-naive children and adolescentswith DSM-IV diagnosis of OCD (mean age: 13.11 ± 3.16; 54.3% males) were included. Standard questionnaires were administered for assessing the study variables. Insight and comorbidities were assessed based on clinician’s interview. Subjects were categorized as belonging to a high insight or a low insight group, and the differences between these two groups were analyzed using ANOVA. Pearson’s correlation coefficients were calculated for the remaining variables of interest. Mediation analysis was carried out using structural equation modeling. Results Relative to those in the high insight group, subjects in the low insight group were younger, had more severe disease and symptoms, and were accommodated to a greater extent by their families. In addition, comorbid depression was more frequent in subjects belonging to the low insight group. Family accommodation was positively related to disease severity, symptom severity, and functional impairment. Family accommodation totally mediated the relationship between symptom severity and functional impairment. Conclusions Results support the differences in the diagnostic criteria between adult and pediatric patients with OCD with respect to the requirement of insight. Subjects with low insight displayed clinical characteristics of increased severity compared with their high insight counterparts, suggesting that subjects with low insight may require multimodal approach to treatment. Family accommodation was found to mediate the relationship between symptom severity and functional impairment; the use of family-based approaches to cognitive behavioral therapy, with one of the aims of reducing/mitigating FA, may provide better treatment outcomes in pediatric OCD. PMID:23786761

A Simulator for the Respiratory Tree in Healthy Subjects Derived from Continued Fractions Expansions

NASA Astrophysics Data System (ADS)

Muntean, Ionuţ; Ionescu, Clara; Naşcu, Ioan

2009-04-01

Taking into account the self-similar recurrent geometrical structure of the human respiratory tree, the total respiratory impedance can be represented using an electrical equivalent of a ladder network model. In this paper, the parameters of the respiratory tree are employed in simulation, based on clinical insight and morphology. Once the transfer function of the total input impedance model is calculated, it is further interpreted in its continued fraction expansion form. The purpose is to compare the ladder network structure with the continuous fraction expansion form of the impedance. The results are supporting the theory of fractional-order impedance appearance (also known as constant-phase behaviour) and help understanding the mathematical and morphological basis for constructing a physiology-based simulator of the human lungs.

Pyromania and the primal scene: a psychoanalytic comment on the work of Yukio Mishima.

PubMed

Arlow, J A

1978-01-01

In the writings of the Japanese novelist, Yukio Mishima, primal scene experiences and derivative expressions of them recur persistently. The element of fire figures prominently in connection with the wish to wreak vengeance on the persons originally observed in the act of intercourse. As a destructive, attention-compelling spectacle, fire is a particularly suitable vehicle for this purpose. In Mishima's works, revenge takes the form of retaliation in kind: parental figures, or their surrogates, are put into the position of having to observe the child, or substitutes for him, in the act of sexual infidelity. These observations as well as clinical reports in the literature suggest some insights into fantasies of pyromania. They also make possible certain speculations concerning Misima's turbulent life and dramatic suicide.

A theory of human error

NASA Technical Reports Server (NTRS)

Mcruer, D. T.; Clement, W. F.; Allen, R. W.

1981-01-01

Human errors tend to be treated in terms of clinical and anecdotal descriptions, from which remedial measures are difficult to derive. Correction of the sources of human error requires an attempt to reconstruct underlying and contributing causes of error from the circumstantial causes cited in official investigative reports. A comprehensive analytical theory of the cause-effect relationships governing propagation of human error is indispensable to a reconstruction of the underlying and contributing causes. A validated analytical theory of the input-output behavior of human operators involving manual control, communication, supervisory, and monitoring tasks which are relevant to aviation, maritime, automotive, and process control operations is highlighted. This theory of behavior, both appropriate and inappropriate, provides an insightful basis for investigating, classifying, and quantifying the needed cause-effect relationships governing propagation of human error.

Publishing data from electronic health records while preserving privacy: a survey of algorithms.

PubMed

Gkoulalas-Divanis, Aris; Loukides, Grigorios; Sun, Jimeng

2014-08-01

The dissemination of Electronic Health Records (EHRs) can be highly beneficial for a range of medical studies, spanning from clinical trials to epidemic control studies, but it must be performed in a way that preserves patients' privacy. This is not straightforward, because the disseminated data need to be protected against several privacy threats, while remaining useful for subsequent analysis tasks. In this work, we present a survey of algorithms that have been proposed for publishing structured patient data, in a privacy-preserving way. We review more than 45 algorithms, derive insights on their operation, and highlight their advantages and disadvantages. We also provide a discussion of some promising directions for future research in this area. Copyright © 2014 Elsevier Inc. All rights reserved.

Decreasing self-reported cognitive biases and increasing clinical insight through meta-cognitive training in patients with chronic schizophrenia.

PubMed

Gawęda, Łukasz; Krężołek, Martyna; Olbryś, Joanna; Turska, Agnieszka; Kokoszka, Andrzej

2015-09-01

The aim of this study was to assess the impact of meta-cognitive training (MCT) on cognitive biases, symptoms, clinical insight, and general functioning among low-level functioning persons diagnosed with chronic schizophrenia who were attending a daily Community Social Support Group Program; we compared the treatment-as-usual (TAU) condition with the MCT + TAU condition. Forty-four patients diagnosed with chronic schizophrenia were allocated to either the MCT + treatment-as-usual condition or the treatment-as-usual (TAU) condition. Delusion and hallucination severity, cognitive biases, clinical insight, and global functioning were assessed pre- and post-treatment (clinical trial NCT02187692). No significant changes were found in symptom severity as measured with the PSYRATS. Conversely, a medium to large effect size was observed for delusional ideation changes when assessed by the self-report measure (Paranoia Checklist). MCT was found to ameliorate cognitive biases as measured by the self-report scale at large effect size, however, no changes in jumping to conclusions (the Fish Task) and theory of mind deficits ("Reading the Mind in the Eyes" Test) were found in the behavioral tasks. MCT increased insight at large effect size. No changes in global functioning were found between the two conditions. Low intensity intervention. No follow-up assessment was provided. Only PSYRATS was assessed blind to patient allocation. MCT has a beneficial effect on low-functioning chronic schizophrenic patients in ameliorating cognitive biases and increasing clinical insight. Copyright © 2015 Elsevier Ltd. All rights reserved.

Impact of interpersonal factors on insight in schizophrenia.

PubMed

Hélène, Tastet; Hélène, Verdoux; Jean, Bouisson; Jean-Marc, Destaillats; Antoinette, Prouteau

2014-11-01

Whereas clinical insight in schizophrenia has been consistently associated with personal factors (i.e. sociodemographic characteristics, symptoms or cognition), little is known about its relationships with interpersonal factors (i.e. close environment and personal characteristics involved in social interactions). Most of the few studies available have focused on one particular interpersonal factor, such as social cognition, contact frequencies or therapeutic alliance. To date, no study has explored the specificity of associations between clinical insight and different levels of interpersonal factors, neither if these associations are independent of personal factors. Associations between insight and interpersonal factors were explored through multiple regression in a sample of 80 outpatients with schizophrenia spectrum disorders. Lower insight was associated with lower interpersonal functioning, independently from personal factors such as age, gender, age at first hospitalization, executive functioning and symptoms. Our findings replicate previous studies with regard to the associations between clinician-rated insight and social cognition or social contact frequencies. They also provide new information about specific associations between clinician-rated insight and perceived social support as well as between patient-rated insight and therapeutic alliance. Finally, models of insight based on personal factors were significantly improved by the inclusion of interpersonal factors. These results strongly support the crucial role of interpersonal factors in insight, both from the clinician's and the patient's point of view. These exploratory data require further replication. Copyright © 2014 Elsevier B.V. All rights reserved.

Is good insight associated with depression among patients with schizophrenia? Systematic review and meta-analysis.

PubMed

Belvederi Murri, Martino; Respino, Matteo; Innamorati, Marco; Cervetti, Alice; Calcagno, Pietro; Pompili, Maurizio; Lamis, Dorian A; Ghio, Lucio; Amore, Mario

2015-03-01

Among patients with schizophrenia, better insight may be associated with depression, but the findings on this issue are mixed. We examined the association between insight and depression in schizophrenia by conducting a systematic review and meta-analysis. The meta-analysis was based on 59 correlational studies and showed that global clinical insight was associated weakly, but significantly with depression (effect size r=0.14), as were the insight into the mental disorder (r=0.14), insight into symptoms (r=0.14), and symptoms' attributions (r=0.17). Conversely, neither insight into the social consequences of the disorder nor into the need for treatment was associated with symptoms of depression. Better cognitive insight was significantly associated with higher levels of depression. The exploratory meta-regression showed that methodological factors (e.g. the instrument used to assess depression and the phase of the illness) can significantly influence the magnitude of the association between insight and depression. Moreover, results from longitudinal studies suggest that the relation between insight and depression might be stronger than what is observed at the cross-sectional level. Finally, internalized stigma, illness perception, recovery attitudes, ruminative style, and premorbid adjustment seem to be relevant moderators and/or mediators of the association between insight and depression. In conclusion, literature indicates that among patients with schizophrenia, better insight is associated with higher levels of depressive symptoms. Thus, interventions aimed at promoting patients' insight should take into account the clinical implications of these findings. Copyright © 2015 Elsevier B.V. All rights reserved.

[Relationship of insight with depression and suicidal ideation in psychotic disorders].

PubMed

Patelaros, E; Zournatzis, E; Kontstantakopoulos, G

2015-01-01

The associations of insight into psychosis (i.e., awareness of illness) with clinical variables have been examined by a great number of studies. Most of these studies revealed that the level of insight is negatively correlated with psychotic symptoms but positively correlated with depression and suicidal ideation. The aim of this study was to test these findings in a Greek sample of patients. Forty-three outpatients (30 men and 13 women) with schizophrenia or delusional disorder being followed up at the Mental Health Centre of Kavala took part in the study. Patients with bipolar or schizoaffective disorder were excluded. Patients' mean age was 40.7 years and the mean duration of illness was 18.67 years. All participants were under treatment and clinically stable at the time of the study. We used the Positive and Negative Syndrome Scale (PANSS) for the assessment of positive and negative symptoms, the Schedule for the Assessment of Insight-Expanded (SAI-E) to assess the insight into psychosis, and the Montgomery-Asberg Depression Rating Scale (MADRS) for the evaluation of depression recording separately the score for item 10 as an estimate of suicidal ideation. All the scales used have been adapted to Greek population. We used Spearman rho coefficient to assess the strength of correlations between the scales because the distributions of some scores were not normal. In order to assess the predictive value of insight for depression and suicidal ideation, we used hierarchical linear regression analysis. Correlation coefficients between SAI-E and the clinical scales of psychopathology, depression and suicide ideation was statistically significant at the p<0.01 level. The correlations between the clinical scales and the three subscales of SAI-E were also significant at the aforementioned p level. The regression analysis showed that our model of positive and negative psychopathology and insight explained 47.4% of the variance of depression and 32.2% of the variance of suicidal ideation. The predictive value of insight was critically important, because only after the introduction of the SAI-E score in the analysis our regression models reached statistical significance. Taking into account its limitations regarding the sample size and the chronicity of the illness, our study confirms the positive correlation of insight with depression and suicidal ideation, offering support to the psychological model of insight.

Insights on the distribution of substitutions in spruce galactoglucomannan and its derivatives using integrated chemo-enzymatic deconstruction, chromatography and mass spectrometry.

PubMed

Liu, Jun; Leppänen, Ann-Sofie; Kisonen, Victor; Willför, Stefan; Xu, Chunlin; Vilaplana, Francisco

2018-06-01

Accurate determination of the distribution of substitutions in the primary molecular structure of heteropolysaccharides and their derivatives is a prerequisite for their increasing application in the pharmaceutical and biomedical fields, which is unfortunately hindered due to the lack of effective analytical techniques. Acetylated galactoglucomannan (GGM) is an abundant plant polysaccharide as the main hemicellulose in softwoods, and therefore constitutes an important renewable resource from lignocellulosic biomass for the development of bioactive and functional materials. Here we present a methodology for profiling the intramolecular structure of spruce GGM and its chemical derivatives (cationic, anionic, and benzoylated) by combining chemo-enzymatic hydrolysis, liquid chromatography, and mass spectrometry. Fast identification and qualitative mass profiling of GGM and its derivatives was conducted using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-ToF-MS) and electrospray ionization mass spectrometry (ESI-MS). Tandem mass fragmentation analysis and its hyphenation with hydrophilic interaction liquid chromatography (HILIC-ESI-MS/MS) provide further insights on the substitution placement of the GGM oligosaccharides and its derivatives. This method will be useful in understanding the structure-function relationships of native GGM and their derivatives, and therefore facilitate their potential application. Copyright © 2018 Elsevier B.V. All rights reserved.

Considerations for animal models of blast-related traumatic brain injury and chronic traumatic encephalopathy.

PubMed

Goldstein, Lee E; McKee, Ann C; Stanton, Patric K

2014-01-01

The association of military blast exposure and brain injury was first appreciated in World War I as commotio cerebri, and later as shell shock. Similar injuries sustained in modern military conflicts are now classified as mild traumatic brain injury (TBI). Recent research has yielded new insights into the mechanisms by which blast exposure leads to acute brain injury and chronic sequelae, including postconcussive syndrome, post-traumatic stress disorder, post-traumatic headache, and chronic traumatic encephalopathy, a tau protein neurodegenerative disease. Impediments to delivery of effective medical care for individuals affected by blast-related TBI include: poor insight into the heterogeneity of neurological insults induced by blast exposure; limited understanding of the mechanisms by which blast exposure injures the brain and triggers sequelae; failure to appreciate interactive injuries that affect frontal lobe function, pituitary regulation, and neurovegetative homeostasis; unknown influence of genetic risk factors, prior trauma, and comorbidities; absence of validated diagnostic criteria and clinical nosology that differentiate clinical endophenotypes; and lack of empirical evidence to guide medical management and therapeutic intervention. While clinicopathological analysis can provide evidence of correlative association, experimental use of animal models remains the primary tool for establishing causal mechanisms of disease. However, the TBI field is confronted by a welter of animal models with varying clinical relevance, thereby impeding scientific coherence and hindering translational progress. Animal models of blast TBI will be far more translationally useful if experimental emphasis focuses on accurate reproduction of clinically relevant endpoints (output) rather than scaled replication of idealized blast shockwaves (input). The utility of an animal model is dependent on the degree to which the model recapitulates pathophysiological mechanisms, neuropathological features, and neurological sequelae observed in the corresponding human disorder. Understanding the purpose of an animal model and the criteria by which experimental results derived from the model are validated are critical components for useful animal modeling. Animal models that reliably demonstrate clinically relevant endpoints will expedite development of new treatments, diagnostics, preventive measures, and rehabilitative strategies for individuals affected by blast TBI and its aftermath.

Considerations for animal models of blast-related traumatic brain injury and chronic traumatic encephalopathy

PubMed Central

2014-01-01

The association of military blast exposure and brain injury was first appreciated in World War I as commotio cerebri, and later as shell shock. Similar injuries sustained in modern military conflicts are now classified as mild traumatic brain injury (TBI). Recent research has yielded new insights into the mechanisms by which blast exposure leads to acute brain injury and chronic sequelae, including postconcussive syndrome, post-traumatic stress disorder, post-traumatic headache, and chronic traumatic encephalopathy, a tau protein neurodegenerative disease. Impediments to delivery of effective medical care for individuals affected by blast-related TBI include: poor insight into the heterogeneity of neurological insults induced by blast exposure; limited understanding of the mechanisms by which blast exposure injures the brain and triggers sequelae; failure to appreciate interactive injuries that affect frontal lobe function, pituitary regulation, and neurovegetative homeostasis; unknown influence of genetic risk factors, prior trauma, and comorbidities; absence of validated diagnostic criteria and clinical nosology that differentiate clinical endophenotypes; and lack of empirical evidence to guide medical management and therapeutic intervention. While clinicopathological analysis can provide evidence of correlative association, experimental use of animal models remains the primary tool for establishing causal mechanisms of disease. However, the TBI field is confronted by a welter of animal models with varying clinical relevance, thereby impeding scientific coherence and hindering translational progress. Animal models of blast TBI will be far more translationally useful if experimental emphasis focuses on accurate reproduction of clinically relevant endpoints (output) rather than scaled replication of idealized blast shockwaves (input). The utility of an animal model is dependent on the degree to which the model recapitulates pathophysiological mechanisms, neuropathological features, and neurological sequelae observed in the corresponding human disorder. Understanding the purpose of an animal model and the criteria by which experimental results derived from the model are validated are critical components for useful animal modeling. Animal models that reliably demonstrate clinically relevant endpoints will expedite development of new treatments, diagnostics, preventive measures, and rehabilitative strategies for individuals affected by blast TBI and its aftermath. PMID:25478023

Large-Scale Wearable Sensor Deployment in Parkinson's Patients: The Parkinson@Home Study Protocol.

PubMed

Silva de Lima, Ana Lígia; Hahn, Tim; de Vries, Nienke M; Cohen, Eli; Bataille, Lauren; Little, Max A; Baldus, Heribert; Bloem, Bastiaan R; Faber, Marjan J

2016-08-26

Long-term management of Parkinson's disease does not reach its full potential because we lack knowledge about individual variations in clinical presentation and disease progression. Continuous and longitudinal assessments in real-life (ie, within the patients' own home environment) might fill this knowledge gap. The primary aim of the Parkinson@Home study is to evaluate the feasibility and compliance of using multiple wearable sensors to collect clinically relevant data. Our second aim is to address the usability of these data for answering clinical research questions. Finally, we aim to build a database for future validation of novel algorithms applied to sensor-derived data from Parkinson's patients during daily functioning. The Parkinson@Home study is a two-phase observational study involving 1000 Parkinson's patients and 250 physiotherapists. Disease status is assessed using a short version of the Parkinson's Progression Markers Initiative protocol, performed by certified physiotherapists. Additionally, participants will wear a set of sensors (smartwatch, smartphone, and fall detector), and use these together with a customized smartphone app (Fox Insight), 24/7 for 3 months. The sensors embedded within the smartwatch and fall detector may be used to estimate physical activity, tremor, sleep quality, and falls. Medication intake and fall incidents will be measured via patients' self-reports in the smartphone app. Phase one will address the feasibility of the study protocol. In phase two, mathematicians will distill relevant summary statistics from the raw sensor signals, which will be compared against the clinical outcomes. Recruitment of 300 participants for phase one was concluded in March, 2016, and the follow-up period will end in June, 2016. Phase two will include the remaining participants, and will commence in September, 2016. The Parkinson@Home study is expected to generate new insights into the feasibility of integrating self-collected information from wearable sensors into both daily routines and clinical practices for Parkinson's patients. This study represents an important step towards building a reliable system that translates and integrates real-life information into clinical decisions, with the long-term aim of delivering personalized disease management support. ClinicalTrials.gov NCT02474329; https://clinicaltrials.gov/ct2/show/NCT02474329 (Archived at http://www.webcitation.org/6joEc5P1v).

Dynamics of competitive systems with a single common limiting factor.

PubMed

Kon, Ryusuke

2015-02-01

The concept of limiting factors (or regulating factors) succeeded in formulating the well-known principle of competitive exclusion. This paper shows that the concept of limiting factors is helpful not only to formulate the competitive exclusion principle, but also to obtain other ecological insights. To this end, by focusing on a specific community structure, we study the dynamics of Kolmogorov equations and show that it is possible to derive an ecologically insightful result only from the information about interactions between species and limiting factors. Furthermore, we find that the derived result is a generalization of the preceding work by Shigesada, Kawasaki, and Teramoto (1984), who examined a certain Lotka-Volterra equation in a different context.

Recent Neurobiological Insights into the Concept of Insight in Psychosis

PubMed Central

Mythri, Starlin Vijay; Sanjay, Y

2016-01-01

The concept of insight in psychosis has been an interesting area in clinical psychiatry for well over a century with a surge in research interest over the past 25 years. Moreover, the past 5 years have been particularly fruitful in deciphering its neurobiological underpinnings. This article presents the development of the concept of insight in psychosis and reviews the current neurobiological research findings in this area. PMID:27335512

Insight and subjective measures of quality of life in chronic schizophrenia.

PubMed

Siu, Cynthia O; Harvey, Philip D; Agid, Ofer; Waye, Mary; Brambilla, Carla; Choi, Wing-Kit; Remington, Gary

2015-09-01

Lack of insight is a well-established phenomenon in schizophrenia, and has been associated with reduced rater-assessed functional performance but increased self-reported well-being in previous studies. The objective of this study was to examine factors that might influence insight (as assessed by the Insight and Treatment Attitudes Questionnaire [ITAQ] or PANSS item G12) and subjective quality-of-life (as assessed by Lehman QoL Interview [LQOLI]), using the large National Institute of Mental Health Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) dataset. Uncooperativeness was assessed by PANSS item G8 ("Uncooperativeness"). In the analysis, we found significant moderating effects for insight on the relationships of subjective life satisfaction assessment to symptom severity (as assessed by CGI-S score), objective everyday functioning (as assessed by rater-administered Heinrichs-Carpenter Quality of Life scale), clinically rated uncooperativeness (as assessed by PANSS G8), and discontinuation of treatment for all causes (all P > 0.05 for statistical interaction between insight and subject QoL). Patients with chronic schizophrenia who reported being "pleased" or "delighted" on LQOLI were found to have significantly lower neurocognitive reasoning performance and poorer insight (ITAQ total score). Our findings underscore the importance of reducing cognitive and insight impairments for both treatment compliance and improved functional outcomes.

The relationship between theory of mind and insight in obsessive-compulsive disorder.

PubMed

Tulacı, Rıza Gökçer; Cankurtaran, Eylem Şahin; Özdel, Kadir; Öztürk, Nefise; Kuru, Erkan; Özdemir, İlker

2018-02-09

It is known that obsessive-compulsive disorder (OCD) patients with poor insight display more severe neuropsychological impairments than other patients with OCD. There are limited studies of OCD and theory of mind (ToM). To investigate ToM skills in patients with OCD and the relationship between insight and ToM skills by comparing OCD patients with good and poor insight. Eighty patients with OCD and 80 healthy controls completed the structured clinical interview for DSM-IV axis I disorders, the Yale Brown Obsessive-Compulsive Scale, the Beck Anxiety and Beck Depression Inventories, and the Brown Assessment of Beliefs Scale. To assess ToM skills, first- and second-order false-belief tests, a hinting test, a faux pas test, a reading the mind in the eyes test, and a double-bluff test were administered. Patients with OCD had poorer ToM abilities than healthy controls. All ToM scores were significantly lower in the poor insight group than in the good insight group (p < .001). A significant negative correlation was found between the BABS-total scores and all the ToM test mean scores (p < .05). The finding of significantly lower ToM skills in OCD with poor insight than in OCD with good insight may contribute to the idea of OCD with poor insight being a subtype with different clinical and neuropsychological characteristics.

A Cross-sectional, Comparative Study of Insight in Schizophrenia and Bipolar Patients in Remission.

PubMed

Ramachandran, Arul Saravanan; Ramanathan, Rajkumar; Praharaj, Samir Kumar; Kanradi, Haridas; Sharma, Podila Satya Venkata Narasimha

2016-01-01

To study insight correlates in schizophrenia and bipolar mood disorder in remission among out-patients attending the Psychiatry Department of a Tertiary Care Hospital. In a cross-sectional, naturalistic study, adult patients with schizophrenia and bipolar mood disorder in remission (n = 80; schizophrenia-40, mania-20, bipolar depression-20) were compared on insight measures and clinical correlates. Scale to Assess the Unawareness of Mental Disorders (SUMD) was used as the main tool to assess current and past measures of insight. Hogan's Drug Attitude Inventory was used to assess the drug attitude and compliance. Positive and Negative Symptom Scale for Schizophrenia, Young's Mania Rating Scale, and HAMD were used to rate psychopathology. Clinical Global Improvement was used as a screening tool for remission. For comparison of the three clinical groups, analysis of variance and Chi-square test were used. In the post-hoc analysis, the Ryan-Einot-Gabriel-Welsch test was used to find the group difference. About 40% in the schizophrenia group were unaware of their mental illness as against none in the bipolar group. The awareness of mental disorder for the current period, the awareness of the achieved effects of medications, and the awareness of social consequence was better in the bipolar group. The drug attitude (compliant positive attitude) increased as the SUMD item scale decreased or in other words, as the insight improved. Insight, both current and retrospect, showed significant differences between the schizophrenia and bipolar patients. Insight is significantly correlated with the observed compliance and drug attitude of the patient groups.

Genetic correlates of insight in schizophrenia.

PubMed

Xavier, Rose Mary; Vorderstrasse, Allison; Keefe, Richard S E; Dungan, Jennifer R

2018-05-01

Insight in schizophrenia is clinically important as it is associated with several adverse outcomes. Genetic contributions to insight are unknown. We examined genetic contributions to insight by investigating if polygenic risk scores (PRS) and candidate regions were associated with insight. Schizophrenia case-only analysis of the Clinical Antipsychotics Trials of Intervention Effectiveness trial. Schizophrenia PRS was constructed using Psychiatric Genomics Consortium (PGC) leave-one out GWAS as discovery data set. For candidate regions, we selected 105 schizophrenia-associated autosomal loci and 11 schizophrenia-related oligodendrocyte genes. We used regressions to examine PRS associations and set-based testing for candidate analysis. We examined data from 730 subjects. Best-fit PRS at p-threshold of 1e-07 was associated with total insight (R 2 =0.005, P=0.05, empirical P=0.054) and treatment insight (R 2 =0.005, P=0.048, empirical P=0.048). For models that controlled for neurocognition, PRS significantly predicted treatment insight but at higher p-thresholds (0.1 to 0.5) but did not survive correction. Patients with highest polygenic burden had 5.9 times increased risk for poor insight compared to patients with lowest burden. PRS explained 3.2% (P=0.002, empirical P=0.011) of variance in poor insight. Set-based analyses identified two variants associated with poor insight- rs320703, an intergenic variant (within-set P=6e-04, FDR P=0.046) and rs1479165 in SOX2-OT (within-set P=9e-04, FDR P=0.046). To the best of our knowledge, this is the first study examining genetic basis of insight. We provide evidence for genetic contributions to impaired insight. Relevance of findings and necessity for replication are discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

microRNA Expression Profiling: Technologies, Insights, and Prospects.

PubMed

Roden, Christine; Mastriano, Stephen; Wang, Nayi; Lu, Jun

2015-01-01

Since the early days of microRNA (miRNA) research, miRNA expression profiling technologies have provided important tools toward both better understanding of the biological functions of miRNAs and using miRNA expression as potential diagnostics. Multiple technologies, such as microarrays, next-generation sequencing, bead-based detection system, single-molecule measurements, and quantitative RT-PCR, have enabled accurate quantification of miRNAs and the subsequent derivation of key insights into diverse biological processes. As a class of ~22 nt long small noncoding RNAs, miRNAs present unique challenges in expression profiling that require careful experimental design and data analyses. We will particularly discuss how normalization and the presence of miRNA isoforms can impact data interpretation. We will present one example in which the consideration in data normalization has provided insights that helped to establish the global miRNA expression as a tumor suppressor. Finally, we discuss two future prospects of using miRNA profiling technologies to understand single cell variability and derive new rules for the functions of miRNA isoforms.

Acute and chronic craniofacial pain: brainstem mechanisms of nociceptive transmission and neuroplasticity, and their clinical correlates.

PubMed

Sessle, B J

2000-01-01

This paper reviews the recent advances in knowledge of brainstem mechanisms related to craniofacial pain. It also draws attention to their clinical implications, and concludes with a brief overview and suggestions for future research directions. It first describes the general organizational features of the trigeminal brainstem sensory nuclear complex (VBSNC), including its input and output properties and intrinsic characteristics that are commensurate with its strategic role as the major brainstem relay of many types of somatosensory information derived from the face and mouth. The VBSNC plays a crucial role in craniofacial nociceptive transmission, as evidenced by clinical, behavioral, morphological, and electrophysiological data that have been especially derived from studies of the relay of cutaneous nociceptive afferent inputs through the subnucleus caudalis of the VBSNC. The recent literature, however, indicates that some fundamental differences exist in the processing of cutaneous vs. other craniofacial nociceptive inputs to the VBSNC, and that rostral components of the VBSNC may also play important roles in some of these processes. Modulatory mechanisms are also highlighted, including the neurochemical substrate by which nociceptive transmission in the VBSNC can be modulated. In addition, the long-term consequences of peripheral injury and inflammation and, in particular, the neuroplastic changes that can be induced in the VBSNC are emphasized in view of the likely role that central sensitization, as well as peripheral sensitization, can play in acute and chronic pain. The recent findings also provide new insights into craniofacial pain behavior and are particularly relevant to many approaches currently in use for the management of pain and to the development of new diagnostic and therapeutic procedures aimed at manipulating peripheral inputs and central processes underlying nociceptive transmission and its control within the VBSNC.

The Effect of a Self-Reflection and Insight Program on the Nursing Competence of Nursing Students: A Longitudinal Study.

PubMed

Pai, Hsiang-Chu

2015-01-01

Nurses have to solve complex problems for their patients and their families, and as such, nursing care capability has become a focus of attention. The aim of this longitudinal study was to develop a self-reflection practice exercise program for nursing students to be used during clinical practice and to evaluate the effects of this program empirically and longitudinally on change in students' clinical competence, self-reflection, stress, and perceived teaching quality. An additional aim was to determine the predictors important to nursing competence. We sampled 260 nursing students from a total of 377 practicum students to participate in this study. A total of 245 students nurse completed 4 questionnaires, Holistic Nursing Competence Scale, Self-Reflection and Insight Scale, Perceived Stress Scale, and Clinical Teaching Quality Scale, at 2, 4, and 6 months after clinical practice experience. Generalized estimating equation models were used to examine the change in scores on each of the questionnaires. The findings showed that, at 6 months after clinical practice, nursing competence was significantly higher than at 2 and 4 months, was positively related to self-reflection and insight, and was negatively related to practice stress. Nursing students' competence at each time period was positively related to clinical teachers' instructional quality at 4 and 6 months. These results indicate that a clinical practice program with self-reflection learning exercise improves nursing students' clinical competence and that nursing students' self-reflection and perceived practice stress affect their nursing competence. Nursing core competencies are enhanced with a self-reflection program, which helps nursing students to improve self-awareness and decrease stress that may interfere with learning. Further, clinical practice experience, self-reflection and insight, and practice stress are predictors of nursing students' clinical competence. Copyright © 2015 Elsevier Inc. All rights reserved.

Race/Ethnic Differences in the Associations of the Framingham Risk Factors with Carotid IMT and Cardiovascular Events

PubMed Central

Hoefer, Imo E.; Eijkemans, Marinus J. C.; Asselbergs, Folkert W.; Anderson, Todd J.; Britton, Annie R.; Dekker, Jacqueline M.; Engström, Gunnar; Evans, Greg W.; de Graaf, Jacqueline; Grobbee, Diederick E.; Hedblad, Bo; Holewijn, Suzanne; Ikeda, Ai; Kitagawa, Kazuo; Kitamura, Akihiko; de Kleijn, Dominique P. V.; Lonn, Eva M.; Lorenz, Matthias W.; Mathiesen, Ellisiv B.; Nijpels, Giel; Okazaki, Shuhei; O’Leary, Daniel H.; Pasterkamp, Gerard; Peters, Sanne A. E.; Polak, Joseph F.; Price, Jacqueline F.; Robertson, Christine; Rembold, Christopher M.; Rosvall, Maria; Rundek, Tatjana; Salonen, Jukka T.; Sitzer, Matthias; Stehouwer, Coen D. A.; Bots, Michiel L.; den Ruijter, Hester M.

2015-01-01

Background Clinical manifestations and outcomes of atherosclerotic disease differ between ethnic groups. In addition, the prevalence of risk factors is substantially different. Primary prevention programs are based on data derived from almost exclusively White people. We investigated how race/ethnic differences modify the associations of established risk factors with atherosclerosis and cardiovascular events. Methods We used data from an ongoing individual participant meta-analysis involving 17 population-based cohorts worldwide. We selected 60,211 participants without cardiovascular disease at baseline with available data on ethnicity (White, Black, Asian or Hispanic). We generated a multivariable linear regression model containing risk factors and ethnicity predicting mean common carotid intima-media thickness (CIMT) and a multivariable Cox regression model predicting myocardial infarction or stroke. For each risk factor we assessed how the association with the preclinical and clinical measures of cardiovascular atherosclerotic disease was affected by ethnicity. Results Ethnicity appeared to significantly modify the associations between risk factors and CIMT and cardiovascular events. The association between age and CIMT was weaker in Blacks and Hispanics. Systolic blood pressure associated more strongly with CIMT in Asians. HDL cholesterol and smoking associated less with CIMT in Blacks. Furthermore, the association of age and total cholesterol levels with the occurrence of cardiovascular events differed between Blacks and Whites. Conclusion The magnitude of associations between risk factors and the presence of atherosclerotic disease differs between race/ethnic groups. These subtle, yet significant differences provide insight in the etiology of cardiovascular disease among race/ethnic groups. These insights aid the race/ethnic-specific implementation of primary prevention. PMID:26134404

Race/Ethnic Differences in the Associations of the Framingham Risk Factors with Carotid IMT and Cardiovascular Events.

PubMed

Gijsberts, Crystel M; Groenewegen, Karlijn A; Hoefer, Imo E; Eijkemans, Marinus J C; Asselbergs, Folkert W; Anderson, Todd J; Britton, Annie R; Dekker, Jacqueline M; Engström, Gunnar; Evans, Greg W; de Graaf, Jacqueline; Grobbee, Diederick E; Hedblad, Bo; Holewijn, Suzanne; Ikeda, Ai; Kitagawa, Kazuo; Kitamura, Akihiko; de Kleijn, Dominique P V; Lonn, Eva M; Lorenz, Matthias W; Mathiesen, Ellisiv B; Nijpels, Giel; Okazaki, Shuhei; O'Leary, Daniel H; Pasterkamp, Gerard; Peters, Sanne A E; Polak, Joseph F; Price, Jacqueline F; Robertson, Christine; Rembold, Christopher M; Rosvall, Maria; Rundek, Tatjana; Salonen, Jukka T; Sitzer, Matthias; Stehouwer, Coen D A; Bots, Michiel L; den Ruijter, Hester M

2015-01-01

Clinical manifestations and outcomes of atherosclerotic disease differ between ethnic groups. In addition, the prevalence of risk factors is substantially different. Primary prevention programs are based on data derived from almost exclusively White people. We investigated how race/ethnic differences modify the associations of established risk factors with atherosclerosis and cardiovascular events. We used data from an ongoing individual participant meta-analysis involving 17 population-based cohorts worldwide. We selected 60,211 participants without cardiovascular disease at baseline with available data on ethnicity (White, Black, Asian or Hispanic). We generated a multivariable linear regression model containing risk factors and ethnicity predicting mean common carotid intima-media thickness (CIMT) and a multivariable Cox regression model predicting myocardial infarction or stroke. For each risk factor we assessed how the association with the preclinical and clinical measures of cardiovascular atherosclerotic disease was affected by ethnicity. Ethnicity appeared to significantly modify the associations between risk factors and CIMT and cardiovascular events. The association between age and CIMT was weaker in Blacks and Hispanics. Systolic blood pressure associated more strongly with CIMT in Asians. HDL cholesterol and smoking associated less with CIMT in Blacks. Furthermore, the association of age and total cholesterol levels with the occurrence of cardiovascular events differed between Blacks and Whites. The magnitude of associations between risk factors and the presence of atherosclerotic disease differs between race/ethnic groups. These subtle, yet significant differences provide insight in the etiology of cardiovascular disease among race/ethnic groups. These insights aid the race/ethnic-specific implementation of primary prevention.

Agent-based modeling of the interaction between CD8+ T cells and Beta cells in type 1 diabetes.

PubMed

Ozturk, Mustafa Cagdas; Xu, Qian; Cinar, Ali

2018-01-01

We propose an agent-based model for the simulation of the autoimmune response in T1D. The model incorporates cell behavior from various rules derived from the current literature and is implemented on a high-performance computing system, which enables the simulation of a significant portion of the islets in the mouse pancreas. Simulation results indicate that the model is able to capture the trends that emerge during the progression of the autoimmunity. The multi-scale nature of the model enables definition of rules or equations that govern cellular or sub-cellular level phenomena and observation of the outcomes at the tissue scale. It is expected that such a model would facilitate in vivo clinical studies through rapid testing of hypotheses and planning of future experiments by providing insight into disease progression at different scales, some of which may not be obtained easily in clinical studies. Furthermore, the modular structure of the model simplifies tasks such as the addition of new cell types, and the definition or modification of different behaviors of the environment and the cells with ease.

Imaging genetics approach to predict progression of Parkinson's diseases.

PubMed

Mansu Kim; Seong-Jin Son; Hyunjin Park

2017-07-01

Imaging genetics is a tool to extract genetic variants associated with both clinical phenotypes and imaging information. The approach can extract additional genetic variants compared to conventional approaches to better investigate various diseased conditions. Here, we applied imaging genetics to study Parkinson's disease (PD). We aimed to extract significant features derived from imaging genetics and neuroimaging. We built a regression model based on extracted significant features combining genetics and neuroimaging to better predict clinical scores of PD progression (i.e. MDS-UPDRS). Our model yielded high correlation (r = 0.697, p <; 0.001) and low root mean squared error (8.36) between predicted and actual MDS-UPDRS scores. Neuroimaging (from 123 I-Ioflupane SPECT) predictors of regression model were computed from independent component analysis approach. Genetic features were computed using image genetics approach based on identified neuroimaging features as intermediate phenotypes. Joint modeling of neuroimaging and genetics could provide complementary information and thus have the potential to provide further insight into the pathophysiology of PD. Our model included newly found neuroimaging features and genetic variants which need further investigation.

Cortical Thickness and Depressive Symptoms in Cognitively Normal Individuals: The Mayo Clinic Study of Aging.

PubMed

Pink, Anna; Przybelski, Scott A; Krell-Roesch, Janina; Stokin, Gorazd B; Roberts, Rosebud O; Mielke, Michelle M; Knopman, David S; Jack, Clifford R; Petersen, Ronald C; Geda, Yonas E

2017-01-01

Altered cortical thickness has been observed in aging and various neurodegenerative disorders. Furthermore, reduced hippocampal volume has been reported in late-life depression. Even mild depressive symptoms are common in the elderly. However, little is known about the structural MRI measures of depressive symptoms in normal cognitive aging. Thus we sought to examine the association between depressive symptoms with cortical thickness and hippocampal volume as measured by brain MRI among community-dwelling participants. We conducted a cross-sectional study derived from the ongoing population-based Mayo Clinic Study of Aging, involving cognitively normal participants (N = 1,507) aged≥70 years. We observed that depressive symptoms were associated with lower global cortical thickness and lower thickness in specific prefrontal and temporal cortical regions, labeled by FreeSurfer software, version 5.3. As expected, the strength of correlation was very small, given that participants were community-dwelling with only mild depressive symptoms. We did not observe associations between hippocampal volume and depressive symptoms. These findings may provide insight into the structural correlates of mild depressive symptoms in elderly participants.

Engineering long term clinical success of advanced ceramic prostheses.

PubMed

Rekow, Dianne; Thompson, Van P

2007-01-01

Biocompatability and, in some applications, esthetics make all-ceramic prostheses compelling choices but despite significant improvements in materials properties and toughening mechanisms, these still have significant failure rates. Factors that contribute to the degradation in strength and survival include material selection and prosthesis design which set the upper limit for performance. However, fabrication operations introduce damage that can be exacerbated by environmental conditions and clinical function. Using all-ceramic dental crowns as an example, experimentally derived models provide insight into the relationships between materials properties and initial critical loads to failure. Analysis of fabrication operations suggests strategies to minimize damage. Environmental conditions can create viscoplastic flow of supporting components which can contribute additional stress within the prosthesis. Fatigue is a particularly challenging problem, not only providing the energy to propagate existing damage but, when combined with the wet environment, can create new damage modes. While much is known, the influence of these new damage modes has not been completely elucidated. The role of complex prosthesis geometry and its interaction with other factors on damage initiation and propagation has yet to be well characterized.

Graph Theoretical Framework of Brain Networks in Multiple Sclerosis: A Review of Concepts.

PubMed

Fleischer, Vinzenz; Radetz, Angela; Ciolac, Dumitru; Muthuraman, Muthuraman; Gonzalez-Escamilla, Gabriel; Zipp, Frauke; Groppa, Sergiu

2017-11-01

Network science provides powerful access to essential organizational principles of the human brain. It has been applied in combination with graph theory to characterize brain connectivity patterns. In multiple sclerosis (MS), analysis of the brain networks derived from either structural or functional imaging provides new insights into pathological processes within the gray and white matter. Beyond focal lesions and diffuse tissue damage, network connectivity patterns could be important for closely tracking and predicting the disease course. In this review, we describe concepts of graph theory, highlight novel issues of tissue reorganization in acute and chronic neuroinflammation and address pitfalls with regard to network analysis in MS patients. We further provide an outline of functional and structural connectivity patterns observed in MS, spanning from disconnection and disruption on one hand to adaptation and compensation on the other. Moreover, we link network changes and their relation to clinical disability based on the current literature. Finally, we discuss the perspective of network science in MS for future research and postulate its role in the clinical framework. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Inositol as putative integrative treatment for PCOS.

PubMed

Genazzani, Alessandro D

2016-12-01

Studies over the last decade have demonstrated that some polycystic ovary syndrome (PCOS) patients have abnormal insulin sensitivity (insulin resistance), independently from being overweight or obese. This induces the risk of developing type 2 diabetes in such PCOS patients. The use of insulin sensitizers (i.e. metformin), reduces such metabolic, and most hormonal, impairments. As metformin often induces side effects, new integrative strategies have been proposed to treat insulin resistance, such as the use of inositols. Such compounds are mainly represented in humans by two inositol stereoisomers: myo-inositol (MYO) and d-chiro-inositol (DCI). MYO is the precursor of inositol triphosphate, a second messenger that regulates thyroid-stimulating hormone (TSH) and FSH as well as insulin. DCI derives from the conversion of myo-inositol via an insulin-dependent pathway. Several preliminary studies have indicated possible benefits of inositol therapy in PCOS patients, but to date no meta-analysis has been performed. This review aims to give clinical insights for the clinical use of inositol in PCOS. Copyright © 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Potential Use of Human Periapical Cyst-Mesenchymal Stem Cells (hPCy-MSCs) as a Novel Stem Cell Source for Regenerative Medicine Applications

PubMed Central

Tatullo, Marco; Codispoti, Bruna; Pacifici, Andrea; Palmieri, Francesca; Marrelli, Massimo; Pacifici, Luciano; Paduano, Francesco

2017-01-01

Mesenchymal stem cells (MSCs) are attracting growing interest by the scientific community due to their huge regenerative potential. Thus, the plasticity of MSCs strongly suggests the utilization of these cells for regenerative medicine applications. The main issue about the clinical use of MSCs is related to the complex way to obtain them from healthy tissues; this topic has encouraged scientists to search for novel and more advantageous sources of these cells in easily accessible tissues. The oral cavity hosts several cell populations expressing mesenchymal stem cell like-features, furthermore, the access to oral and dental tissues is simple and isolation of cells is very efficient. Thus, oral-derived stem cells are highly attractive for clinical purposes. In this context, human periapical cyst mesenchymal stem cells (hPCy-MSCs) exhibit characteristics similar to other dental-derived MSCs, including their extensive proliferative potential, cell surface marker profile and the ability to differentiate into various cell types such as osteoblasts, adipocytes and neurons. Importantly, hPCy-MSCs are easily collected from the surgically removed periapical cysts; this reusing of biological waste guarantees a smart source of stem cells without any impact on the surrounding healthy tissues. In this review, we report the most interesting research topics related to hPCy-MSCs with a newsworthy discussion about the future insights. This newly discovered cell population exhibits interesting and valuable potentialities that could be of high impact in the future regenerative medicine applications. PMID:29259970

Potential Use of Human Periapical Cyst-Mesenchymal Stem Cells (hPCy-MSCs) as a Novel Stem Cell Source for Regenerative Medicine Applications.

PubMed

Tatullo, Marco; Codispoti, Bruna; Pacifici, Andrea; Palmieri, Francesca; Marrelli, Massimo; Pacifici, Luciano; Paduano, Francesco

2017-01-01

Mesenchymal stem cells (MSCs) are attracting growing interest by the scientific community due to their huge regenerative potential. Thus, the plasticity of MSCs strongly suggests the utilization of these cells for regenerative medicine applications. The main issue about the clinical use of MSCs is related to the complex way to obtain them from healthy tissues; this topic has encouraged scientists to search for novel and more advantageous sources of these cells in easily accessible tissues. The oral cavity hosts several cell populations expressing mesenchymal stem cell like-features, furthermore, the access to oral and dental tissues is simple and isolation of cells is very efficient. Thus, oral-derived stem cells are highly attractive for clinical purposes. In this context, human periapical cyst mesenchymal stem cells (hPCy-MSCs) exhibit characteristics similar to other dental-derived MSCs, including their extensive proliferative potential, cell surface marker profile and the ability to differentiate into various cell types such as osteoblasts, adipocytes and neurons. Importantly, hPCy-MSCs are easily collected from the surgically removed periapical cysts; this reusing of biological waste guarantees a smart source of stem cells without any impact on the surrounding healthy tissues. In this review, we report the most interesting research topics related to hPCy-MSCs with a newsworthy discussion about the future insights. This newly discovered cell population exhibits interesting and valuable potentialities that could be of high impact in the future regenerative medicine applications.

Occupational therapists' self-insight into their referral prioritisation policies for clients with mental health needs.

PubMed

Harries, Priscilla Ann; Gilhooly, Kenneth J

2010-12-01

Obtaining valid accounts of professionals' thinking is dependent upon experts' capacity for self-insight. Self-insight has implications for developing professional decision making, facilitating education and promoting agreement among therapists. The aim of this study was to examine occupational therapists' self-insight into their referral prioritisation policies. A total of 40 occupational therapists individually rated the importance that differing types of referral content had on their prioritisation of referrals. These subjective policies were then correlated with their objective referral prioritisation policies that had been previously statistically derived. Self-insight was found to be moderate but with wide variation across individuals and across referral information used. Self-insight on cues that were important to the decision was found to be better than on those cues not so important to the decision.   Occupational therapists have similar levels of self-insight to other professional groups. The 'attention hypothesis' may explain why self-insight varied across referral information used. © 2010 The Authors. Australian Occupational Therapy Journal © 2010 Australian Association of Occupational Therapists.

Pragmatics in discourse performance: insights from aphasiology.

PubMed

Ulatowska, Hanna K; Olness, Gloria Streit

2007-05-01

This article examines the preservation of pragmatic abilities of individuals with aphasia, as manifested in the discourse they produce. The construct of coherence is used as a framework for understanding this pragmatic preservation. Discourse coherence is largely derived from the structure, selection, and highlighting of information expressed in a discourse. Personal narratives, as one type of discourse, represent an extended turn-in-conversation on a topic of personal relevance to the speaker, common in everyday life. As such, they provide a valuable source of information about a speaker's pragmatic ability. Examples of personal narratives told by individuals with aphasia are used to illustrate and discuss the means by which discourse coherence is achieved. These include a tightly structured temporal-causal event line, development of theme, and evaluation of information. Possible approaches to clinical assessment are considered, including use of global rating systems.

Meaningful lives: elders in treatment for depression.

PubMed

Ragan, Meredith; Kane, Catherine F

2010-12-01

Depression among elderly persons is common. Major depression is disabling, highly prevalent, and adversely affects daily function and quality of life. Although studies have demonstrated that interpersonal psychotherapy (IPT) and medication can relieve the symptoms of depression, many elders do not seek treatment. Of those elders who do participate in treatment experience, 20% to 50% do not experience partial or full relief from depressive symptoms. Improvements in treatment strategies are needed to better serve this population. In this study, 20 elders in treatment for depression with IPT and medication were interviewed to better understand their day-to-day lives. These interviews provided insights and perspectives to inform clinical practice and improve treatment strategies. The major themes identified were independence, spirituality, family, depression, medical comorbidities, and motivation. Potential treatment strategies were derived from these themes. Copyright © 2010 Elsevier Inc. All rights reserved.

Pomegranate extracts and cancer prevention: molecular and cellular activities.

PubMed

Syed, Deeba N; Chamcheu, Jean-Christopher; Adhami, Vaqar M; Mukhtar, Hasan

2013-10-01

There is increased appreciation by the scientific community that dietary phytochemicals can be potential weapons in the fight against cancer. Emerging data has provided new insights into the molecular and cellular framework needed to establish novel mechanism-based strategies for cancer prevention by selective bioactive food components. The unique chemical composition of the pomegranate fruit, rich in antioxidant tannins and flavonoids has drawn the attention of many investigators. Polyphenol rich fractions derived from the pomegranate fruit have been studied for their potential chemopreventive and/or cancer therapeutic effects in several animal models. Although data from in vitro and in vivo studies look convincing, well designed clinical trials in humans are needed to ascertain whether pomegranate can become part of our armamentarium against cancer. This review summarizes the available literature on the effects of pomegranate against various cancers.

Melanocytic nevi and melanoma: unraveling a complex relationship

PubMed Central

Damsky, WE; Bosenberg, M

2018-01-01

Approximately 33% of melanomas are derived directly from benign, melanocytic nevi. Despite this, the vast majority of melanocytic nevi, which typically form as a result of BRAFV600E-activating mutations, will never progress to melanoma. Herein, we synthesize basic scientific insights and data from mouse models with common observations from clinical practice to comprehensively review melanocytic nevus biology. In particular, we focus on the mechanisms by which growth arrest is established after BRAFV600E mutation. Means by which growth arrest can be overcome and how melanocytic nevi relate to melanoma are also considered. Finally, we present a new conceptual paradigm for understanding the growth arrest of melanocytic nevi in vivo termed stable clonal expansion. This review builds upon the canonical hypothesis of oncogene-induced senescence in growth arrest and tumor suppression in melanocytic nevi and melanoma. PMID:28604751

Neurovirulence safety testing of mumps vaccines--historical perspective and current status.

PubMed

Rubin, S A; Afzal, M A

2011-04-05

Many live, attenuated viral vaccines are derived from wild type viruses with known neurovirulent properties. To assure the absence of residual neurotoxicity, pre-clinical neurovirulence safety testing of candidate vaccines is performed. For mumps virus, a highly neurotropic virus, neurovirulence safety testing is performed in monkeys. However, laboratory studies suggest an inability of this test to correctly discern among virus strains of varying neurovirulence potential in man, and, further, some vaccines found to be neuroattenuated in monkeys were later found to be neurovirulent in humans when administered in large numbers. Over the past decade, concerted efforts have been made to replace monkey-based neurovirulence safety testing with more informative, alternative methods. This review summarizes the current status of mumps vaccine neurovirulence safety testing and insights into models currently approved and those under development. Published by Elsevier Ltd.

Pomegranate Extracts and Cancer Prevention: Molecular and Cellular Activities

PubMed Central

Syed, Deeba N.; Chamcheu, Jean-Christopher; Adhami, Vaqar M.; Mukhtar, Hasan

2014-01-01

There is increased appreciation by the scientific community that dietary phytochemicals can be potential weapons in the fight against cancer. Emerging data has provided new insights into the molecular and cellular framework needed to establish novel mechanism-based strategies for cancer prevention by selective bioactive food components. The unique chemical composition of the pomegranate fruit, rich in antioxidant tannins and flavonoids has drawn the attention of many investigators. Polyphenol rich fractions derived from the pomegranate fruit have been studied for their potential chemopreventive and/or cancer therapeutic effects in several animal models. Although data from in vitro and in vivo studies look convincing, well designed clinical trials in humans are needed to ascertain whether pomegranate can become part of our armamentarium against cancer. This review summarizes the available literature on the effects of pomegranate against various cancers. PMID:23094914

Insight into k13-propeller gene polymorphism and ex vivo DHA-response profiles from Cameroonian isolates.

PubMed

Menard, Sandie; Tchoufack, Joëlle Njila; Maffo, Christelle Ngou; Nsango, Sandrine E; Iriart, Xavier; Abate, Luc; Tsapi, Majoline Tchioffo; Awono-Ambéné, Parfait H; Abega Mekongo, Francis A; Morlais, Isabelle; Berry, Antoine

2016-11-26

The spread of Plasmodium falciparum resistance to artemisinin derivatives in Southeast Asia is a major source of concern and the emergence of resistance in Africa would have dramatic consequences, by increasing malaria mortality and morbidity. It is therefore urgent to implement regular monitoring in sentinel sites in sub-Saharan Africa using robust and easy-to-implement tools. The prevalence of k13-propeller mutations and the phenotypic profiles are poorly known in sub-Saharan Africa. Here, the k13-propeller polymorphism was compared to both ex vivo susceptibility to DHA and early parasitological and clinical responses to artemisinin combination therapy (ACT). Plasmodium falciparum isolates were collected in 2015 in Yaoundé (Cameroon) from patients treated with dihydroartemisinin-piperaquine combination. Samples were analysed for their susceptibility to artemisinin using the k13-propeller sequencing, the ex vivo ring-stage survival assay, the in vivo parasite positive rate and the clinical statute at day 2. None of the collected isolates revealed the presence of resistance mutations in the k13-propeller sequence. The median ring-stage survival rate for all the 64 interpretable isolates after a 6-hour pulse of 700 nM dihydroartemisinin was low, 0.49% (IQR: 0-1.3). Total parasite clearance was observed for 87.5% of patients and the remaining parasitaemic isolates (12.5%) showed a high reduction of parasite load, ranging from 97.5 to 99.9%. Clinical symptoms disappeared in 92.8% of cases. This study demonstrated the absence of k13-resistant genotypes in P. falciparum isolates from Cameroon. Only synonymous mutations were found with a low prevalence (4.3%). A good association between k13 genotypes and the ex vivo ring-stage survival assay or parasitological and clinical data was obtained. These results give a baseline for the long-term monitoring of artemisinin derivative efficacy in Africa.

Animal models for bone tissue engineering and modelling disease

PubMed Central

Griffin, Michelle

2018-01-01

ABSTRACT Tissue engineering and its clinical application, regenerative medicine, are instructing multiple approaches to aid in replacing bone loss after defects caused by trauma or cancer. In such cases, bone formation can be guided by engineered biodegradable and nonbiodegradable scaffolds with clearly defined architectural and mechanical properties informed by evidence-based research. With the ever-increasing expansion of bone tissue engineering and the pioneering research conducted to date, preclinical models are becoming a necessity to allow the engineered products to be translated to the clinic. In addition to creating smart bone scaffolds to mitigate bone loss, the field of tissue engineering and regenerative medicine is exploring methods to treat primary and secondary bone malignancies by creating models that mimic the clinical disease manifestation. This Review gives an overview of the preclinical testing in animal models used to evaluate bone regeneration concepts. Immunosuppressed rodent models have shown to be successful in mimicking bone malignancy via the implantation of human-derived cancer cells, whereas large animal models, including pigs, sheep and goats, are being used to provide an insight into bone formation and the effectiveness of scaffolds in induced tibial or femoral defects, providing clinically relevant similarity to human cases. Despite the recent progress, the successful translation of bone regeneration concepts from the bench to the bedside is rooted in the efforts of different research groups to standardise and validate the preclinical models for bone tissue engineering approaches. PMID:29685995

Mindfulness and Emotion Regulation: Insights from Neurobiological, Psychological, and Clinical Studies

PubMed Central

Guendelman, Simón; Medeiros, Sebastián; Rampes, Hagen

2017-01-01

There is increasing interest in the beneficial clinical effects of mindfulness-based interventions (MBIs). Research has demonstrated their efficacy in a wide range of psychological conditions characterized by emotion dysregulation. Neuroimaging studies have evidenced functional and structural changes in a myriad of brain regions mainly involved in attention systems, emotion regulation, and self-referential processing. In this article we review studies on psychological and neurobiological correlates across different empirically derived models of research, including dispositional mindfulness, mindfulness induction, MBIs, and expert meditators in relation to emotion regulation. From the perspective of recent findings in the neuroscience of emotion regulation, we discuss the interplay of top-down and bottom-up emotion regulation mechanisms associated with different mindfulness models. From a phenomenological and cognitive perspective, authors have argued that mindfulness elicits a “mindful emotion regulation” strategy; however, from a clinical perspective, this construct has not been properly differentiated from other strategies and interventions within MBIs. In this context we propose the distinction between top-down and bottom-up mindfulness based emotion regulation strategies. Furthermore, we propose an embodied emotion regulation framework as a multilevel approach for understanding psychobiological changes due to mindfulness meditation regarding its effect on emotion regulation. Finally, based on clinical neuroscientific evidence on mindfulness, we open perspectives and dialogues regarding commonalities and differences between MBIs and other psychotherapeutic strategies for emotion regulation. PMID:28321194

The Potential of GMP-Compliant Platelet Lysate to Induce a Permissive State for Cardiovascular Transdifferentiation in Human Mediastinal Adipose Tissue-Derived Mesenchymal Stem Cells

PubMed Central

Bordin, Antonella; Ponti, Donatella; Iudicone, Paola; Rendina, Erino Angelo; Calogero, Antonella; Pierelli, Luca; Ibrahim, Mohsen; De Falco, Elena

2015-01-01

Human adipose tissue-derived mesenchymal stem cells (ADMSCs) are considered eligible candidates for cardiovascular stem cell therapy applications due to their cardiac transdifferentiation potential and immunotolerance. Over the years, the in vitro culture of ADMSCs by platelet lysate (PL), a hemoderivate containing numerous growth factors and cytokines derived from platelet pools, has allowed achieving a safe and reproducible methodology to obtain high cell yield prior to clinical administration. Nevertheless, the biological properties of PL are still to be fully elucidated. In this brief report we show the potential ability of PL to induce a permissive state of cardiac-like transdifferentiation and to cause epigenetic modifications. RTPCR results indicate an upregulation of Cx43, SMA, c-kit, and Thy-1 confirmed by immunofluorescence staining, compared to standard cultures with foetal bovine serum. Moreover, PL-cultured ADMSCs exhibit a remarkable increase of both acetylated histones 3 and 4, with a patient-dependent time trend, and methylation at lysine 9 on histone 3 preceding the acetylation. Expression levels of p300 and SIRT-1, two major regulators of histone 3, are also upregulated after treatment with PL. In conclusion, PL could unravel novel biological properties beyond its routine employment in noncardiac applications, providing new insights into the plasticity of human ADMSCs. PMID:26495284

The potential of GMP-compliant platelet lysate to induce a permissive state for cardiovascular transdifferentiation in human mediastinal adipose tissue-derived mesenchymal stem cells.

PubMed

Siciliano, Camilla; Chimenti, Isotta; Bordin, Antonella; Ponti, Donatella; Iudicone, Paola; Peruzzi, Mariangela; Rendina, Erino Angelo; Calogero, Antonella; Pierelli, Luca; Ibrahim, Mohsen; De Falco, Elena

2015-01-01

Human adipose tissue-derived mesenchymal stem cells (ADMSCs) are considered eligible candidates for cardiovascular stem cell therapy applications due to their cardiac transdifferentiation potential and immunotolerance. Over the years, the in vitro culture of ADMSCs by platelet lysate (PL), a hemoderivate containing numerous growth factors and cytokines derived from platelet pools, has allowed achieving a safe and reproducible methodology to obtain high cell yield prior to clinical administration. Nevertheless, the biological properties of PL are still to be fully elucidated. In this brief report we show the potential ability of PL to induce a permissive state of cardiac-like transdifferentiation and to cause epigenetic modifications. RTPCR results indicate an upregulation of Cx43, SMA, c-kit, and Thy-1 confirmed by immunofluorescence staining, compared to standard cultures with foetal bovine serum. Moreover, PL-cultured ADMSCs exhibit a remarkable increase of both acetylated histones 3 and 4, with a patient-dependent time trend, and methylation at lysine 9 on histone 3 preceding the acetylation. Expression levels of p300 and SIRT-1, two major regulators of histone 3, are also upregulated after treatment with PL. In conclusion, PL could unravel novel biological properties beyond its routine employment in noncardiac applications, providing new insights into the plasticity of human ADMSCs.

Performance comparison of SNP detection tools with illumina exome sequencing data—an assessment using both family pedigree information and sample-matched SNP array data

PubMed Central

Yi, Ming; Zhao, Yongmei; Jia, Li; He, Mei; Kebebew, Electron; Stephens, Robert M.

2014-01-01

To apply exome-seq-derived variants in the clinical setting, there is an urgent need to identify the best variant caller(s) from a large collection of available options. We have used an Illumina exome-seq dataset as a benchmark, with two validation scenarios—family pedigree information and SNP array data for the same samples, permitting global high-throughput cross-validation, to evaluate the quality of SNP calls derived from several popular variant discovery tools from both the open-source and commercial communities using a set of designated quality metrics. To the best of our knowledge, this is the first large-scale performance comparison of exome-seq variant discovery tools using high-throughput validation with both Mendelian inheritance checking and SNP array data, which allows us to gain insights into the accuracy of SNP calling through such high-throughput validation in an unprecedented way, whereas the previously reported comparison studies have only assessed concordance of these tools without directly assessing the quality of the derived SNPs. More importantly, the main purpose of our study was to establish a reusable procedure that applies high-throughput validation to compare the quality of SNP discovery tools with a focus on exome-seq, which can be used to compare any forthcoming tool(s) of interest. PMID:24831545

On insight and psychosis: discussion paper.

PubMed Central

David, A S

1990-01-01

The concept of insight into psychosis has received scant attention in the psychiatric literature. Various types of insight are described after drawing on such sources as phenomenology, clinical observation and experimental psychology. It is proposed that insight is far from an all or none phenomenon but comprises three overlapping dimensions, namely, the recognition that one has a mental illness, compliance with treatment and the ability to re-label unusual mental events (delusions and hallucinations) as pathological. PMID:2199672

Biomarkers and surrogate endpoints in clinical trials.

PubMed

Fleming, Thomas R; Powers, John H

2012-11-10

One of the most important considerations in designing clinical trials is the choice of outcome measures. These outcome measures could be clinically meaningful endpoints that are direct measures of how patients feel, function, and survive. Alternatively, indirect measures, such as biomarkers that include physical signs of disease, laboratory measures, and radiological tests, often are considered as replacement endpoints or 'surrogates' for clinically meaningful endpoints. We discuss the definitions of clinically meaningful endpoints and surrogate endpoints, and provide examples from recent clinical trials. We provide insight into why indirect measures such as biomarkers may fail to provide reliable evidence about the benefit-to-risk profile of interventions. We also discuss the nature of evidence that is important in assessing whether treatment effects on a biomarker reliably predict effects on a clinically meaningful endpoint, and provide insights into why this reliability is specific to the context of use of the biomarker. Copyright © 2012 John Wiley & Sons, Ltd.

Biomarkers and Surrogate Endpoints In Clinical Trials

PubMed Central

Fleming, Thomas R.; Powers, John H

2012-01-01

One of the most important considerations in designing clinical trials is the choice of outcome measures. These outcome measures could be clinically meaningful endpoints that are direct measures of how patients feel, function and survive. Alternatively, indirect measures, such as biomarkers that include physical signs of disease, laboratory measures and radiological tests, often are considered as replacement endpoints or “surrogates” for clinically meaningful endpoints. We discuss the definitions of clinically meaningful endpoints and surrogate endpoints, and provide examples from recent clinical trials. We provide insight into why indirect measures such as biomarkers may fail to provide reliable evidence about the benefit-to-risk profile of interventions. We also discuss the nature of evidence that is important in assessing whether treatment effects on a biomarker reliably predict effects on a clinically meaningful endpoint, and provide insights into why this reliability is specific to the context of use of the biomarker. . PMID:22711298

The mediating role of insight for long-term improvements in psychodynamic therapy.

PubMed

Johansson, Paul; Høglend, Per; Ulberg, Randi; Amlo, Svein; Marble, Alice; Bøgwald, Kjell-Petter; Sørbye, Oystein; Sjaastad, Mary Cosgrove; Heyerdahl, Oscar

2010-06-01

According to psychoanalytic theory, interpretation of transference leads to increased insight that again leads to improved interpersonal functioning over time. In this study, we performed a full mediational analysis to test whether insight gained during treatment mediates the long-term effects of transference interpretation in dynamic psychotherapy. This study is a randomized clinical trial with a dismantling design. One hundred outpatients seeking psychotherapy for depression, anxiety, personality disorders, and interpersonal problems were randomly assigned to 1 year of weekly sessions of dynamic psychotherapy with transference interpretation or to the same type and duration of treatment with the same therapists but without the use of transference interpretation. Interpersonal functioning and insight were measured pretreatment, posttreatment, and 1 year and 3 years after treatment termination. Contrary to common expectation, patients with a life-long pattern of low quality of object relations and personality disorder pathology profited more from therapy with transference interpretation than from therapy with no transference interpretation. This long-term effect was mediated by an increase in the level of insight during treatment. Insight seems to be a key mechanism of change in dynamic psychotherapy. Our results bridge the gap between clinical theory and empirical research.

Outcome of first-episode schizophrenia in India: longitudinal study of effect of insight and psychopathology.

PubMed

Saravanan, Balasubramanian; Jacob, K S; Johnson, Shanthi; Prince, Martin; Bhugra, Dinesh; David, Anthony S

2010-06-01

Transcultural studies have found lack of insight to be an almost invariable feature of acute and chronic schizophrenia, but its influence on prognosis is unclear. To investigate the relationship between insight, psychopathology and outcome of first-episode schizophrenia in Vellore, India. Patients with a DSM-IV diagnosis of schizophrenia (n = 131) were assessed prospectively at baseline and at 6-month and 12-month follow-up. Demographic and clinical measures included insight, psychopathology, duration of untreated psychosis (DUP) and social functioning. Linear and logistic regression was used to measure predictors of outcome. Follow-up data were available for 115 patients at 1 year. All achieved remission, half of them with and half without residual symptoms. Changes in psychopathology and insight during the first 6 months and DUP strongly predicted outcome (relapse or functional impairment), controlling for baseline measures. Outcome of schizophrenia in this setting is driven by early symptomatic improvement and is relatively favourable, in line with other studies from low- and middle-income countries. Early improvement in insight might be a useful clinical guide to future outcome. Reduction of DUP should be a target for intervention.

Advances in Clinical and Biomedical Applications of Photoacoustic Imaging

PubMed Central

Su, Jimmy L.; Wang, Bo; Wilson, Katheryne E.; Bayer, Carolyn L.; Chen, Yun-Sheng; Kim, Seungsoo; Homan, Kimberly A.; Emelianov, Stanislav Y.

2010-01-01

Importance of the field Photoacoustic imaging is an imaging modality that derives image contrast from the optical absorption coefficient of the tissue being imaged. The imaging technique is able to differentiate between healthy and diseased tissue with either deeper penetration or higher resolution than other functional imaging modalities currently available. From a clinical standpoint, photoacoustic imaging has demonstrated safety and effectiveness in diagnosing diseased tissue regions using either endogenous tissue contrast or exogenous contrast agents. Furthermore, the potential of photoacoustic imaging has been demonstrated in various therapeutic interventions ranging from drug delivery and release to image-guided therapy and monitoring. Areas covered in this review This article reviews the current state of photoacoustic imaging in biomedicine from a technological perspective, highlights various biomedical and clinical applications of photoacoustic imaging, and gives insights on future directions. What the reader will gain Readers will learn about the various applications of photoacoustic imaging, as well as the various contrast agents that can be used to assist photoacoustic imaging. This review will highlight both pre-clinical and clinical uses for photoacoustic imaging, as well as discuss some of the challenges that must be addressed to move photoacoustic imaging into the clinical realm. Take home message Photoacoustic imaging offers unique advantages over existing imaging modalities. The imaging field is broad with many exciting applications for detecting and diagnosing diseased tissue or processes. Photoacoustics is also used in therapeutic applications to identify and characterize the pathology and then to monitor the treatment. Although the technology is still in its infancy, much work has been done in the pre-clinical arena, and photoacoustic imaging is fast approaching the clinical setting. PMID:21344060

Methodological inaccuracies in clinical aortic valve severity assessment: insights from computational fluid dynamic modeling of CT-derived aortic valve anatomy

NASA Astrophysics Data System (ADS)

Traeger, Brad; Srivatsa, Sanjay S.; Beussman, Kevin M.; Wang, Yechun; Suzen, Yildirim B.; Rybicki, Frank J.; Mazur, Wojciech; Miszalski-Jamka, Tomasz

2016-04-01

Aortic stenosis is the most common valvular heart disease. Assessing the contribution of the valve as a portion to total ventricular load is essential for the aging population. A CT scan for one patient was used to create one in vivo tricuspid aortic valve geometry and assessed with computational fluid dynamics (CFD). CFD simulated the pressure, velocity, and flow rate, which were used to assess the Gorlin formula and continuity equation, current clinical diagnostic standards. The results demonstrate an underestimation of the anatomic orifice area (AOA) by Gorlin formula and overestimation of AOA by the continuity equation, using peak velocities, as would be measured clinically by Doppler echocardiography. As a result, we suggest that the Gorlin formula is unable to achieve the intended estimation of AOA and largely underestimates AOA at the critical low-flow states present in heart failure. The disparity in the use of echocardiography with the continuity equation is due to the variation in velocity profile between the outflow tract and the valve orifice. Comparison of time-averaged orifice areas by Gorlin and continuity with instantaneous orifice areas by planimetry can mask the errors of these methods, which is a result of the assumption that the blood flow is inviscid.

Clinical laboratory assessments for Mycoplasma genitalium in a high-prevalence sexually-transmitted infection community reveal epidemiologic dichotomies with Trichomonas vaginalis.

PubMed

Munson, Erik; Munson, Kimber L; Schell, Ronald F

2017-02-01

Mycoplasma genitalium is an emerging agent of sexually-transmitted infection and is responsible for clinically-significant genital tract disease in both females and males. Similar to scenarios recently experienced with the urogenital flagellate Trichomonas vaginalis, an evolving molecular diagnostic reference standard based on transcription-mediated amplification allows for accurate detection of the organism, plus additional insight into disease epidemiology. Areas covered. The basis for this article includes primary peer-reviewed literature plus compilations of data derived from routine clinical laboratory screening of females and males for agents of sexually-transmitted infection. Introductory laboratory and epidemiologic data related to T. vaginalis provides not only a foreshadowing to the dichotomies inherent to M. genitalium prevalence but also advocacy of a common non-invasive specimen source that could be used to screen females for both agents. This review also documents increased prevalence rates of M. genitalium in both females and males by way of transcription-mediated amplification. Expert commentary. Molecular detection of M. genitalium should be a consideration in the development of comprehensive sexually-transmitted infection screening programs for both females and males. Transcription-mediated amplification has additionally identified novel facets of M. genitalium and T. vaginalis epidemiology that warrant further investigation.

A Modeling Insight into Adipose-Derived Stem Cell Myogenesis.

PubMed

Deshpande, Rajiv S; Grayson, Warren L; Spector, Alexander A

2015-01-01

Adipose-derived stem cells (ASCs) are clinically important in regenerative medicine as they are relatively easy to obtain, are characterized by low morbidity, and can differentiate into myogenic progenitor cells. Although studies have elucidated the principal markers, PAX7, Desmin, MyoD, and MHC, the underlying mechanisms are not completely understood. This motivates the application of computational methods to facilitate greater understanding of such processes. In the following, we present a multi-stage kinetic model comprising a system of ordinary differential equations (ODEs). We sought to model ASC differentiation using data from a static culture, where no strain is applied, and a dynamic culture, where 10% strain is applied. The coefficients of the equations have been modulated by those experimental data points. To correctly represent the trajectories, various switches and a feedback factor based on total cell number have been introduced to better represent the biology of ASC differentiation. Furthermore, the model has then been applied to predict ASC fate for strains different from those used in the experimental conditions and for times longer than the duration of the experiment. Analysis of the results reveals unique characteristics of ASC myogenesis under dynamic conditions of the applied strain.

Scientific biography, cognitive deficits, and laboratory practice. James McKeen Cattell and early American experimental psychology, 1880-1904.

PubMed

Sokal, Michael M

2010-09-01

Despite widespread interest in individual life histories, few biographies of scientists make use of insights derived from psychology, another discipline that studies people, their thoughts, and their actions. This essay argues that recent theoretical work in psychology and tools developed for clinical psychological practice can help biographical historians of science create and present fuller portraits of their subjects' characters and temperaments and more nuanced analyses of how these traits helped shape their subjects' scientific work. To illustrate this thesis, the essay examines the early career of James McKeen Cattell--an influential late nineteenth- and early twentieth-century experimental psychologist--through a lens offered by psychology and argues that Cattell's actual laboratory practices derived from an "accommodation" to a long-standing "cognitive deficit." These practices in turn enabled Cattell to achieve more precise experimental results than could any of his contemporaries; and their students readily adopted them, along with their behavioral implications. The essay concludes that, in some ways, American psychology's early twentieth-century move toward a behavioral understanding of psychological phenomena can be traced to Cattell's personal cognitive deficit. It closes by reviewing several "remaining general questions" that this thesis suggests.

Facile one-pot multicomponent synthesis and molecular docking studies of steroidal oxazole/thiazole derivatives with effective antimicrobial, antibiofilm and hemolytic properties.

PubMed

Ansari, Anam; Ali, Abad; Asif, Mohd; Rauf, Mohd Ahmar; Owais, Mohammad; Shamsuzzaman

2018-06-01

A series of steroidal oxazole and thiazole derivatives have been synthesized employing thiosemicarbazide/semicarbazide hydrochloride and ethyl 2-chloroacetoacetate with a simple and facile one-pot multicomponent reaction pathway. The antimicrobial activity of newly synthesized compounds were evaluated against four bacterial strains namely Gram-negative (Escherichia coliand Pseudomonas aeruginosa) and Gram-positive bacteria (Staphylococcus aureus and Listeria monocytogenes) in addition to pathogenic fungi (Candida albicans and Cryptococcus neoformans). Bioactivity assay manifested that most of the compounds exhibited good antimicrobial activity. To provide additional insight into antimicrobial activity, the compounds were also tested for their antibiofilm activity against S. aureus biofilm. Moreover, molecular docking study shows binding of compounds with amino acid residues of DNA gyrase and glucosamine-6-phosphate synthase (promising antimicrobial target) through hydrogen bonding interactions. Hemolytic activity have been also investigated to ascertain the effect of compounds over RBC lysis and results indicate good prospects for biocompatibility. The expedient synthesis of steroidal heterocycles, effective antibacterial and antifungal behavior against various clinically relevant human pathogens, promising biocompatibility offer opportunities for further modification and potential applications as therapeutic agents. Copyright © 2018 Elsevier Inc. All rights reserved.

Recombinant Allergens in Structural Biology, Diagnosis, and Immunotherapy

PubMed Central

Tscheppe, Angelika; Breiteneder, Heimo

2017-01-01

The years 1988–1995 witnessed the beginning of allergen cloning and the generation of recombinant allergens, which opened up new avenues for the diagnosis and research of human allergic diseases. Most crystal and solution structures of allergens have been obtained using recombinant allergens. Structural information on allergens allows insights into their evolutionary biology, illustrates clinically observed cross-reactivities, and makes the design of hypoallergenic derivatives for allergy vaccines possible. Recombinant allergens are widely used in molecule-based allergy diagnosis such as protein microarrays or suspension arrays. Recombinant technologies have been used to produce well-characterized, noncontaminated vaccine components with known biological activities including a variety of allergen derivatives with reduced IgE reactivity. Such recombinant hypoallergens as well as wild-type recombinant allergens have been used successfully in several immunotherapy trials for more than a decade to treat birch and grass pollen allergy. As a more recent application, the development of antibody repertoires directed against conformational epitopes during immunotherapy has been monitored by recombinant allergen chimeras. Although much progress has been made, the number and quality of recombinant allergens will undoubtedly increase and keep improving our knowledge in basic scientific investigations, diagnosis, and therapy of human allergic diseases. PMID:28467993

Computational study of some benzamidine-based inhibitors of thrombin-like snake venom proteinases

NASA Astrophysics Data System (ADS)

Henriques, Elsa S.; Nascimento, Marco A. C.; Ramos, Maria João

Pit viper venoms contain a number of serine proteinases that, despite their observed coagulant thrombin-like action in vitro, exhibit a paradoxical benign defibrinogenating (anticoagulant) action in vivo, with clinical applications in preventing thrombi and improved blood circulation. Considering that several benzamidine-based inhibitors, some highly selective to thrombin, also inhibit the enzymatic activity of such venombins, the modeling of their enzyme-inhibitor interactions could provide valuable information on the topological factors that determine the divergences in activity. The first step, and the object of the present study, was to derive the necessary set of parameters, consistent with the CHARMM force field, and to perform molecular dynamics (MD) simulations on a few selected representatives of the inhibitors in question under physiological conditions. Bonding and van der Waals parameters were derived by analogy to similar ones in the existing force field. Net atomic charges were obtained with a restrained fitting to the molecular electrostatic potential generated at B3LYP/6-31G(d) level. The parameters were refined to reproduce the available experimental geometries and crystal data, and the MD simulations of the free inhibitors in aqueous solution at 298 K provided an insightful description of their available conformational space.

Medications Development for the Treatment of Alcohol Use Disorder: Insights into the Predictive Value of Animal and Human Laboratory Models

PubMed Central

Yardley, Megan M.; Ray, Lara A.

2016-01-01

Development of effective treatments for alcohol use disorder (AUD) represents an important public health goal. This review provides a summary of completed preclinical and clinical studies testing pharmacotherapies for treatment of AUD. We discuss opportunities for improving the translation from preclinical findings to clinical trial outcomes, focusing on the validity and predictive value of animal and human laboratory models of AUD. Specifically, while preclinical studies of medications development have offered important insights into the neurobiology of the disorder and alcohol's molecular targets, limitations include the lack of standardized methods and streamlined processes whereby animal studies can readily inform human studies. Behavioral pharmacology studies provide a less expensive and valuable opportunity to assess the feasibility of a pharmacotherapy prior to initiating larger scale clinical trials by providing insights into the mechanism of the drug, which can then inform recruitment, analyses, and assessments. Summary tables are provided to illustrate the wide range of preclinical, human laboratory, and clinical studies of medications development for alcoholism. Taken together, this review highlights the challenges associated with animal paradigms, human laboratory studies and clinical trials with the overarching goal of advancing treatment development and highlighting opportunities to bridge the gap between preclinical and clinical research. PMID:26833803

Catalog of genetic progression of human cancers: breast cancer.

PubMed

Desmedt, Christine; Yates, Lucy; Kulka, Janina

2016-03-01

With the rapid development of next-generation sequencing, deeper insights are being gained into the molecular evolution that underlies the development and clinical progression of breast cancer. It is apparent that during evolution, breast cancers acquire thousands of mutations including single base pair substitutions, insertions, deletions, copy number aberrations, and structural rearrangements. As a consequence, at the whole genome level, no two cancers are identical and few cancers even share the same complement of "driver" mutations. Indeed, two samples from the same cancer may also exhibit extensive differences due to constant remodeling of the genome over time. In this review, we summarize recent studies that extend our understanding of the genomic basis of cancer progression. Key biological insights include the following: subclonal diversification begins early in cancer evolution, being detectable even in in situ lesions; geographical stratification of subclonal structure is frequent in primary tumors and can include therapeutically targetable alterations; multiple distant metastases typically arise from a common metastatic ancestor following a "metastatic cascade" model; systemic therapy can unmask preexisting resistant subclones or influence further treatment sensitivity and disease progression. We conclude the review by describing novel approaches such as the analysis of circulating DNA and patient-derived xenografts that promise to further our understanding of the genomic changes occurring during cancer evolution and guide treatment decision making.

Sex Differences in Functional Stress Test Versus CT Angiography in Symptomatic Patients With Suspected CAD: Insights From PROMISE

PubMed Central

Pagidipati, Neha J.; Hemal, Kshipra; Coles, Adrian; Mark, Daniel B.; Dolor, Rowena J.; Pellikka, Patricia A.; Hoffmann, Udo; Litwin, Sheldon E.; Udelson, James; Daubert, Melissa A.; Shah, Svati H.; Martinez, Beth; Lee, Kerry L.; Douglas, Pamela S.

2016-01-01

Background Risk stratification is an important goal of cardiac noninvasive tests (NITs), yet little contemporary data exist on the prognostic value of different NITs by patient sex. Objectives To compare the results and prognostic information derived from anatomic versus stress testing in stable men and women with suspected coronary artery disease. Methods In 8966 PROMISE trial patients tested as randomized (4500 computed tomographic angiography [CTA], 52% female; 4466 stress testing, 53% female), we assessed the relationship between sex and NIT results using logistic regression, and the relationship between sex and a composite of death, myocardial infarction, and unstable angina hospitalization using Cox proportional hazards models. Results In women, a positive CTA (≥70% stenosis) was less likely than a positive stress test (8% vs. 12%, adjusted OR 0.67 [95% CI 0.55-0.82]). Compared with negative tests, a positive CTA was more strongly associated with subsequent clinical events than a positive stress test (CTA adjusted HR 5.86 [95% CI 3.32-10.35]; stress adjusted HR 2.27 [95% CI 1.21-4.25]; adjusted p=0.028). Men were more likely to have a positive CTA than stress test (16% vs. 14%, adjusted OR 1.23 [95% CI 1.04-1.47]). Compared with negative tests, a positive CTA was less strongly associated with subsequent clinical events than a positive stress test in men, although this difference was not statistically significant (CTA adjusted HR 2.80 [95% CI 1.76-4.45]; stress adjusted HR 4.42 [95% CI 2.77-7.07]; adjusted p=0.168). Negative CTA and stress tests were equally likely to predict an event in both sexes (adjusted p-values=NS). A significant interaction between sex, NIT type, and test result (p=0.01) suggests that sex and NIT type jointly influence the relationship between test result and clinical events. Conclusions The prognostic value of an NIT result varies by test type and patient sex. Women appear to derive more prognostic information from a CTA, while men tend to derive similar prognostic value from both test types. PMID:27058908

Intermolecular interaction of thiosemicarbazone derivatives to solvents and a potential Aedes aegypti target

NASA Astrophysics Data System (ADS)

da Silva, João Bosco P.; Hallwass, Fernando; da Silva, Aluizio G.; Moreira, Diogo Rodrigo; Ramos, Mozart N.; Espíndola, José Wanderlan P.; de Oliveira, Ana Daura T.; Brondani, Dalci José; Leite, Ana Cristina L.; Merz, Kenneth M.

2015-08-01

DFT calculations were used to access information about structure, energy and electronic properties of series of phenyl- and phenoxymethyl-(thio)semicarbazone derivatives with demonstrated activity against the larvae of Aedes aegypti in stage L4. The way as the thiosemicarbazone derivatives can interact with solvents like DMSO and water were analyzed from the comparison between calculated and experimental 1H NMR chemical shifts. The evidences of thiosemicarbazone derivatives making H-bond interaction to solvent have provide us insights on how they can interact with a potential A. aegypti's biological target, the Sterol Carrier Protein-2.

INSIGHT AGONISTES: A READING OF SOPHOCLES'S OEDIPUS THE KING.

PubMed

Mahon, Eugene J

2015-07-01

In this reading of Sophocles's Oedipus the King, the author suggests that insight can be thought of as the main protagonist of the tragedy. He personifies this depiction of insight, calling it Insight Agonistes, as if it were the sole conflicted character on the stage, albeit masquerading at times as several other characters, including gods, sphinxes, and oracles. This psychoanalytic reading of the text lends itself to an analogy between psychoanalytic process and Sophocles's tragic hero. The author views insight as always transgressing against, always at war with a conservative, societal, or intrapsychic chorus of structured elements. A clinical vignette is presented to illustrate this view of insight. © 2015 The Psychoanalytic Quarterly, Inc.

Market Orientation within University Schools of Business: Can a Dynamical Systems Viewpoint Applied to a Non-Temporal Data Set Yield Valuable Insights for University Managers?

ERIC Educational Resources Information Center

Cox, John C.; Webster, Robert L.; Hammond, Kevin L.

2009-01-01

This study investigates the use of using complexity theory--the study of nonlinear dynamical systems of which chaos and catastrophe theory are subsets--in the analysis of a non temporal data set to derive valuable insights into the functioning of university schools of business. The approach is unusual in that studies of nonlinearity in complex…

Narrative insight in psychosis: The relationship with spiritual and religious explanatory frameworks.

PubMed

Marriott, Michael R; Thompson, Andrew R; Cockshutt, Graham; Rowse, Georgina

2018-03-25

When considering psychosis, the concept of narrative insight has been offered as an alternative to clinical insight in determining individuals' responses to their difficulties, as it allows for a more holistic and person-centred framework to be embraced within professional practice. This study aims to explore the validity of the narrative insight construct within a group of people who have experienced psychosis. Inductive qualitative methods were used to explore how eight participants utilized spiritual or religious explanatory frameworks for their experiences of psychosis and to consider these in relation to the construct of narrative insight. Semi-structured interviews were undertaken with individuals who identified themselves as interested in spiritual or religious ideas and whose self-reported experiences which were identified as akin to psychosis by experienced academic clinicians. Transcriptions from these interviews were subject to interpretative phenomenological analysis within a broader research question; a selection of themes and data from the resultant phenomenological structure are explored here for their relevance to narrative insight. Participants discussed spiritual and biological explanations for their experiences and were able to hold alternative potential explanations alongside each other. They were reflective regarding the origins of their explanations and would describe a process of testing and proof in relation to them. These findings suggest that the narrative insight construct has the potential to be a valid approach to understanding experiences of psychosis, and challenge the dominance of the clinical insight construct within clinical practice. Clinicians should value the explanatory framework for experiences which are provided by individuals experiencing psychosis, and encourage them to develop a framework which is coherent to their own world view rather than predominantly pursuing a biomedical explanation. Assessments of psychosis should be adapted to include an understanding of the cohesiveness of the individual's explanatory framework and personal value to them, with a reduced focus on their acceptance of biomedical models of 'illness'. Care and care research for individuals experiencing psychosis should consider the value of narrative insight within future developments. © 2018 The Authors. Psychology and Psychotherapy: Theory, Research and Practice published by John Wiley & Sons Ltd on behalf of British Psychological Society.

Metacognitive capacity as a predictor of insight in first-episode psychosis.

PubMed

Vohs, Jenifer L; Lysaker, Paul H; Liffick, Emily; Francis, Michael M; Leonhardt, Bethany L; James, Alison; Buck, Kelly D; Hamm, Jay A; Minor, Kyle S; Mehdiyoun, Nikki; Breier, Alan

2015-05-01

Impaired insight is common in the first episode of psychosis (FEP). Although considerable research has examined the factors that are associated with impaired insight in chronic psychosis, less is known about the factors that underlie and sustain poor insight in FEP. Impaired metacognition, or the ability to form integrated representations of self and others, is a promising potential contributor to poor insight in FEP. To explore this possibility, the authors assessed insight and metacognition in 40 individuals with FEP and then examined the relationship between these areas and social cognition domains, neurocognitive domains, and psychotic symptoms. Correlation analyses revealed that improved insight was associated with higher metacognition, better vocabulary and Theory of Mind scores, and fewer symptoms. The domain of metacognitive mastery also predicted clinical insight. Results support the need to develop an integrative therapeutic approach focused on improving metacognition, hence addressing poor insight in FEP.

The impact of insight in a first-episode mania with psychosis population on outcome at 18 months.

PubMed

Smith, Leo T; Shelton, Clare L; Berk, Michael; Hasty, Melissa K; Cotton, Sue M; Henry, Lisa; Daglas, Rothanthi; Gentle, Ellen; McGorry, Patrick D; Macneil, Craig A; Conus, Philippe

2014-01-01

To explore whether poor initial insight during a first episode of mania with psychotic features was predictive of poor psychosocial and clinical outcomes at 18 months. Secondary analysis was performed on data collected during an 8-week RCT comparing the efficacy of olanzapine versus chlorpromazine as an adjunct to lithium, and at 18-month follow-up. 74 participants were divided into three groups (no insight, partial insight, and full insight) according to the insight item from the Young Mania Rating Scale (YMRS). Differences between these three groups were examined at baseline and at 18 months on measures of symptoms (YMRS, HAMD-21, and CGI-S), and social and occupational functioning (SOFAS). Baseline differences between the three groups were determined using general linear models and chi-squared analyses. Group differences from baseline to 18-month follow-up were determined using repeated measures general linear models. At baseline there were significant differences between the three insight groups in terms of mania and functioning, but at 18 months all groups had improved significantly in terms of psychopathology, mania, depression and social and occupational functioning. There were no significant differences between the three groups at study completion with respect to these domains. The study was limited by the lack of availability of a more detailed rating scale for insight, and it did not account for the duration of untreated psychosis (DUI). Poor initial insight during a first episode of mania with psychotic features does not predict poor clinical and psychosocial outcome at 18 months. Crown Copyright © 2014. Published by Elsevier B.V. All rights reserved.

Characterization, isolation and culture of primordial germ cells in domestic animals: recent progress and insights from the ovine species.

PubMed

Ledda, S; Bogliolo, L; Bebbere, D; Ariu, F; Pirino, S

2010-09-01

Primordial germ cell (PGC) allocation, characterization, lineage restriction, and differentiation have been extensively studied in the mouse. Murine PGC can be easily identified using markers as alkaline phosphatase content or the expression of pluripotent markers such as Pou5f1, Nanog, Sox2, Kit, SSEA1, and SSEA4. These tools allowed us to clarify certain aspects of the complex interactions of somatic and germinal cells in the establishment of the germ cell lineage, its segregation from the neighbouring somatic tissue, and the guidance mechanisms during migration that direct most of the germ cells into the genital ridges. Few data are available from other domestic animals and here we reported our preliminary studies on the isolation, characterization, and in vitro culture of sheep PGCs. Sheep PGCs can be identified with the markers previously used in mouse, but, in some cases, these markers are not coherently expressed in the same cell depending on the grade of differentiation and on technical problems related to commercial antibodies used. Pluripotency of PGCs in culture (EGCs) from domestic animals also needs further evaluation even though the derivation of embryonic pluripotent cell lines from large mammals may be an advantage as they are more physiologically similar to the human and perhaps more relevant for clinical translation studies. Comprehensive epigenetic reprogramming of the genome in early germ cells, and derived EGCs including extensive erasure of epigenetic modifications, may be relevant for gaining insight into events that lead to reprogramming and establishment of totipotency. EGCs can differentiate in vitro in a various range of tissues, form embryonic bodies, but in many cases failed to generate tumours when transplanted into immunodeficient mice and are not able to generate germline chimeric animals after their transfer. Such incomplete information clearly indicates the urge to improve the studies on derivation of stem cells in farm animals and shows the need for a multidisciplinary investigation in order to create farm animal models to set up suitable ethical and technical systems for cell regenerative therapies in humans. Copyright 2010 Elsevier Inc. All rights reserved.

Mental capacity, diagnosis and insight in psychiatric in-patients: a cross-sectional study.

PubMed

Owen, G S; David, A S; Richardson, G; Szmukler, G; Hayward, P; Hotopf, M

2009-08-01

Mental capacity is now a core part of UK mental health law and clinicians will increasingly be expected to assess it. Because it is a legal concept there is a need to clarify associations with variables that clinicians are more familiar with, especially insight. In this cross-sectional study we recruited consecutive psychiatric admissions to the Maudsley Hospital, London. We carried out structured assessments of decision making using the MacArthur Competence Assessment Tool for Treatment (MacCAT-T), resulting in a clinical judgement about capacity status. We analysed associations with a range of sociodemographic and clinical variables, including insight score on the Expanded Schedule for the Assessment of Insight (SAI-E). The same variables were compared in an analysis stratified according to diagnostic group: psychotic disorders/bipolar affective disorder (BPAD)/non-psychotic disorders. Psychotic disorders and manic episodes of BPAD are most strongly associated with incapacity. In such patients, insight is the best discriminator of capacity status. In patients with non-psychotic disorders, insight is less strongly associated with capacity; in this group depressed mood discriminates capacity status whereas it does not in psychotic disorders. Cognitive performance does not discriminate capacity status in patients with psychotic disorders. Mental capacity has complex relationships with psychopathological variables, and these relationships are different according to diagnostic group. Insight is the best discriminator of capacity status in psychotic disorders and BPAD but not in non-psychotic disorders.

Word-finding difficulty: a clinical analysis of the progressive aphasias

PubMed Central

Rohrer, Jonathan D.; Knight, William D.; Warren, Jane E.; Fox, Nick C.; Rossor, Martin N.; Warren, Jason D.

2008-01-01

The patient with word-finding difficulty presents a common and challenging clinical problem. The complaint of ‘word-finding difficulty’ covers a wide range of clinical phenomena and may signify any of a number of distinct pathophysiological processes. Although it occurs in a variety of clinical contexts, word-finding difficulty generally presents a diagnostic conundrum when it occurs as a leading or apparently isolated symptom, most often as the harbinger of degenerative disease: the progressive aphasias. Recent advances in the neurobiology of the focal, language-based dementias have transformed our understanding of these processes and the ways in which they breakdown in different diseases, but translation of this knowledge to the bedside is far from straightforward. Speech and language disturbances in the dementias present unique diagnostic and conceptual problems that are not fully captured by classical models derived from the study of vascular and other acute focal brain lesions. This has led to a reformulation of our understanding of how language is organized in the brain. In this review we seek to provide the clinical neurologist with a practical and theoretical bridge between the patient presenting with word-finding difficulty in the clinic and the evidence of the brain sciences. We delineate key illustrative speech and language syndromes in the degenerative dementias, compare these syndromes with the syndromes of acute brain damage, and indicate how the clinical syndromes relate to emerging neurolinguistic, neuroanatomical and neurobiological insights. We propose a conceptual framework for the analysis of word-finding difficulty, in order both better to define the patient's complaint and its differential diagnosis for the clinician and to identify unresolved issues as a stimulus to future work. PMID:17947337

CPTAC Investigators Discuss Research Insights and Perspectives as part of ASBMB Journal Club - 12 Nov | Office of Cancer Clinical Proteomics Research

Cancer.gov

On Wednesday, November 12, 2014 from 2:00 PM to 3:00 PM EST, Daniel Liebler, PhD (Vanderbilt University) and Karin Rodland, PhD (Pacific Northwestern National Laboratory) and Ruedi Aebersold, PhD (Swiss Federal Institute of Technology) will share their research insight as part of the ASBMB Journal Club.  Both Doctors Liebler and Rodland are Principal Investigators in the NCI’s Clinical Proteomic Tumor Analysis Consortium.

Morphometricity as a measure of the neuroanatomical signature of a trait.

PubMed

Sabuncu, Mert R; Ge, Tian; Holmes, Avram J; Smoller, Jordan W; Buckner, Randy L; Fischl, Bruce

2016-09-27

Complex physiological and behavioral traits, including neurological and psychiatric disorders, often associate with distributed anatomical variation. This paper introduces a global metric, called morphometricity, as a measure of the anatomical signature of different traits. Morphometricity is defined as the proportion of phenotypic variation that can be explained by macroscopic brain morphology. We estimate morphometricity via a linear mixed-effects model that uses an anatomical similarity matrix computed based on measurements derived from structural brain MRI scans. We examined over 3,800 unique MRI scans from nine large-scale studies to estimate the morphometricity of a range of phenotypes, including clinical diagnoses such as Alzheimer's disease, and nonclinical traits such as measures of cognition. Our results demonstrate that morphometricity can provide novel insights about the neuroanatomical correlates of a diverse set of traits, revealing associations that might not be detectable through traditional statistical techniques.

Textural analysis of optical coherence tomography skin images: quantitative differentiation between healthy and cancerous tissues

NASA Astrophysics Data System (ADS)

Adabi, Saba; Conforto, Silvia; Hosseinzadeh, Matin; Noe, Shahryar; Daveluy, Steven; Mehregan, Darius; Nasiriavanaki, Mohammadreza

2017-02-01

Optical Coherence Tomography (OCT) offers real-time high-resolution three-dimensional images of tissue microstructures. In this study, we used OCT skin images acquired from ten volunteers, neither of whom had any skin conditions addressing the features of their anatomic location. OCT segmented images are analyzed based on their optical properties (attenuation coefficient) and textural image features e.g., contrast, correlation, homogeneity, energy, entropy, etc. Utilizing the information and referring to their clinical insight, we aim to make a comprehensive computational model for the healthy skin. The derived parameters represent the OCT microstructural morphology and might provide biological information for generating an atlas of normal skin from different anatomic sites of human skin and may allow for identification of cell microstructural changes in cancer patients. We then compared the parameters of healthy samples with those of abnormal skin and classified them using a linear Support Vector Machines (SVM) with 82% accuracy.

Retinoids activate the irritant receptor TRPV1 and produce sensory hypersensitivity

PubMed Central

Yin, Shijin; Luo, Jialie; Qian, Aihua; Du, Junhui; Yang, Qing; Zhou, Shentai; Yu, Weihua; Du, Guangwei; Clark, Richard B.; Walters, Edgar T.; Carlton, Susan M.; Hu, Hongzhen

2013-01-01

Retinoids are structurally related derivatives of vitamin A and are required for normal vision as well as cell proliferation and differentiation. Clinically, retinoids are effective in treating many skin disorders and cancers. Application of retinoids evokes substantial irritating side effects, including pain and inflammation; however, the precise mechanisms accounting for the sensory hypersensitivity are not understood. Here we show that both naturally occurring and synthetic retinoids activate recombinant or native transient receptor potential channel vanilloid subtype 1 (TRPV1), an irritant receptor for capsaicin, the pungent ingredient of chili peppers. In vivo, retinoids produced pain-related behaviors that were either eliminated or significantly reduced by genetic or pharmacological inhibition of TRPV1 function. These findings identify TRPV1 as an ionotropic receptor for retinoids and provide cellular and molecular insights into retinoid-evoked hypersensitivity. These findings also suggest that selective TRPV1 antagonists are potential therapeutic drugs for treating retinoid-induced sensory hypersensitivity. PMID:23925292

Analytical modeling of drug dynamics induced by eluting stents in the coronary multi-layered curved domain.

PubMed

d'Errico, Michele; Sammarco, Paolo; Vairo, Giuseppe

2015-09-01

Pharmacokinetics induced by drug eluting stents (DES) in coronary walls is modeled by means of a one-dimensional multi-layered model, accounting for vessel curvature and non-homogeneous properties of the arterial tissues. The model includes diffusion mechanisms, advection effects related to plasma filtration through the walls, and bio-chemical drug reactions. A non-classical Sturm-Liouville problem with discontinuous coefficients is derived, whose closed-form analytical solution is obtained via an eigenfunction expansion. Soundness and consistency of the proposed approach are shown by numerical computations based on possible clinical treatments involving both hydrophilic and hydrophobic drugs. The influence of the main model parameters on drug delivery mechanisms is analyzed, highlighting the effects induced by vessel curvature and yielding comparative indications and useful insights into the concurring mechanisms governing the pharmacokinetics. Copyright © 2015. Published by Elsevier Inc.

Is AMH a regulator of follicular atresia?

PubMed

Seifer, David B; Merhi, Zaher

2014-11-01

We discuss the hypothesis that AMH is an intraovarian regulator that inhibits follicular atresia within the human ovary. Several indirect lines of evidence derived from clinical and basic science studies in a variety of different patient populations and model systems collectively support this hypothesis. Evidence presented herein include 1) timing of onset of menopause in women with polycystic ovary syndrome, 2) site of cellular origin and timing of AMH production, 3) AMH's influence on other critical growth factors and enzymes involved in folliculogenesis, and 4) AMH's inhibition of granulosa apoptosis. If this hypothesis is true, it may provide insight for treatment strategies for prevention and treatment of premature ovarian insufficiency, slowing natural ovarian aging, and/or delaying eventual ovarian failure. Such findings may lead to the development of 1) AMH agonists for retarding the onset of menopause and/or as a chemoprotectant prior to cancer therapy and 2) AMH antagonists for the treatment of PCOS.

An integrated genomic and transcriptomic survey of mucormycosis-causing fungi

PubMed Central

Chibucos, Marcus C.; Soliman, Sameh; Gebremariam, Teclegiorgis; Lee, Hongkyu; Daugherty, Sean; Orvis, Joshua; Shetty, Amol C.; Crabtree, Jonathan; Hazen, Tracy H.; Etienne, Kizee A.; Kumari, Priti; O'Connor, Timothy D.; Rasko, David A.; Filler, Scott G.; Fraser, Claire M.; Lockhart, Shawn R.; Skory, Christopher D.; Ibrahim, Ashraf S.; Bruno, Vincent M.

2016-01-01

Mucormycosis is a life-threatening infection caused by Mucorales fungi. Here we sequence 30 fungal genomes, and perform transcriptomics with three representative Rhizopus and Mucor strains and with human airway epithelial cells during fungal invasion, to reveal key host and fungal determinants contributing to pathogenesis. Analysis of the host transcriptional response to Mucorales reveals platelet-derived growth factor receptor B (PDGFRB) signaling as part of a core response to divergent pathogenic fungi; inhibition of PDGFRB reduces Mucorales-induced damage to host cells. The unique presence of CotH invasins in all invasive Mucorales, and the correlation between CotH gene copy number and clinical prevalence, are consistent with an important role for these proteins in mucormycosis pathogenesis. Our work provides insight into the evolution of this medically and economically important group of fungi, and identifies several molecular pathways that might be exploited as potential therapeutic targets. PMID:27447865

Morphometricity as a measure of the neuroanatomical signature of a trait

PubMed Central

Sabuncu, Mert R.; Ge, Tian; Holmes, Avram J.; Smoller, Jordan W.; Buckner, Randy L.; Fischl, Bruce

2016-01-01

Complex physiological and behavioral traits, including neurological and psychiatric disorders, often associate with distributed anatomical variation. This paper introduces a global metric, called morphometricity, as a measure of the anatomical signature of different traits. Morphometricity is defined as the proportion of phenotypic variation that can be explained by macroscopic brain morphology. We estimate morphometricity via a linear mixed-effects model that uses an anatomical similarity matrix computed based on measurements derived from structural brain MRI scans. We examined over 3,800 unique MRI scans from nine large-scale studies to estimate the morphometricity of a range of phenotypes, including clinical diagnoses such as Alzheimer’s disease, and nonclinical traits such as measures of cognition. Our results demonstrate that morphometricity can provide novel insights about the neuroanatomical correlates of a diverse set of traits, revealing associations that might not be detectable through traditional statistical techniques. PMID:27613854

Introduction to the Theme "New Methods and Novel Therapeutic Approaches in Pharmacology and Toxicology".

PubMed

Insel, Paul A; Amara, Susan G; Blaschke, Terrence F; Meyer, Urs A

2017-01-06

Major advances in scientific discovery and insights can result from the development and use of new techniques, as exemplified by the work of Solomon Snyder, who writes a prefatory article in this volume. The Editors have chosen "New Methods and Novel Therapeutic Approaches in Pharmacology and Toxicology" as the Theme for a number of articles in this volume. These include ones that review the development and use of new experimental tools and approaches (e.g., nanobodies and techniques to explore protein-protein interactions), new types of therapeutics (e.g., aptamers and antisense oligonucleotides), and systems pharmacology, which assembles (big) data derived from omics studies together with information regarding drugs and patients. The application of these new methods and therapeutic approaches has the potential to have a major impact on basic and clinical research in pharmacology and toxicology as well as on patient care.

Lysosome-Dependent Activation of Human Dendritic Cells by the Vaccine Adjuvant QS-21

PubMed Central

Welsby, Iain; Detienne, Sophie; N’Kuli, Francisca; Thomas, Séverine; Wouters, Sandrine; Bechtold, Viviane; De Wit, Dominique; Gineste, Romain; Reinheckel, Thomas; Elouahabi, Abdelatif; Courtoy, Pierre J.; Didierlaurent, Arnaud M.; Goriely, Stanislas

2017-01-01

The adjuvant properties of the saponin QS-21 have been known for decades. It is a component of the Adjuvant System AS01 that is used in several vaccine candidates. QS-21 strongly potentiates both cellular and humoral immune responses to purified antigens, yet how it activates immune cells is largely unknown. Here, we report that QS-21 directly activated human monocyte-derived dendritic cells (moDCs) and promoted a pro-inflammatory transcriptional program. Cholesterol-dependent QS-21 endocytosis followed by lysosomal destabilization and Syk kinase activation were prerequisites for this response. Cathepsin B, a lysosomal cysteine protease, was essential for moDC activation in vitro and contributed to the adjuvant effects of QS-21 in vivo. Collectively, these findings provide new insights into the pathways involved in the direct activation of antigen-presenting cells by a clinically relevant QS-21 formulation. PMID:28105029

Genetic association studies in β-hemoglobinopathies.

PubMed

Thein, Swee Lay

2013-01-01

Characterization of the molecular basis of the β-thalassemias and sickle cell disease (SCD) clearly showed that individuals with the same β-globin genotypes can have extremely diverse clinical severity. Two key modifiers, an innate ability to produce fetal hemoglobin and coinheritance of α-thalassemia, both derived from family and population studies, affect the pathophysiology of both disorders at the primary level. In the past 2 decades, scientific research had applied genetic approaches to identify additional genetic modifiers. The review summarizes recent genetic studies and key genetic modifiers identified and traces the story of fetal hemoglobin genetics, which has led to an emerging network of globin gene regulation. The discoveries have provided insights on new targets for therapeutic intervention and raise possibilities of developing fetal hemoglobin predictive diagnostics for predicting disease severity in the newborn and for integration into prenatal diagnosis to better inform genetic counseling.

Computational analysis of calculated physicochemical and ADMET properties of protein-protein interaction inhibitors

NASA Astrophysics Data System (ADS)

Lagorce, David; Douguet, Dominique; Miteva, Maria A.; Villoutreix, Bruno O.

2017-04-01

The modulation of PPIs by low molecular weight chemical compounds, particularly by orally bioavailable molecules, would be very valuable in numerous disease indications. However, it is known that PPI inhibitors (iPPIs) tend to have properties that are linked to poor Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) and in some cases to poor clinical outcomes. Previously reported in silico analyses of iPPIs have essentially focused on physicochemical properties but several other ADMET parameters would be important to assess. In order to gain new insights into the ADMET properties of iPPIs, computations were carried out on eight datasets collected from several databases. These datasets involve compounds targeting enzymes, GPCRs, ion channels, nuclear receptors, allosteric modulators, oral marketed drugs, oral natural product-derived marketed drugs and iPPIs. Several trends are reported that should assist the design and optimization of future PPI inhibitors, either for drug discovery endeavors or for chemical biology projects.

Mechanistic Insight of Probiotics Derived Anticancer Pharmaceuticals: A Road Forward for Cancer Therapeutics.

PubMed

Kumar, Raman; Dhanda, Suman

2017-04-01

Probiotics are living organisms that confer health benefits when administered in adequate amounts. Probiotics are continuously being explored for their different health beneficiary activities. Anticancer activity is one of the most important benefits both from a preventive and therapeutic point of view. Though not many studies have been conducted to date in this area, a number suggest using laboratory animal models and different cell lines that there may be a mechanistic basis for the anticancer effects of probiotics and require more scientific justification and clinical trials. Most studies of probiotics are conducted for colon cancer associated with inflammatory bowel disease. Studies are also being extended to other types of cancer in different cell lines. This review summarizes studied probiotics considered for treatment of colon cancer and some other cancers (in cancer cell lines) and also proposed mechanism how probiotics are inhibiting cancer growth along with some challenges and future perspectives.

Islam and the four principles of medical ethics.

PubMed

Mustafa, Yassar

2014-07-01

The principles underpinning Islam's ethical framework applied to routine clinical scenarios remain insufficiently understood by many clinicians, thereby unfortunately permitting the delivery of culturally insensitive healthcare.This paper summarises the foundations of the Islamic ethical theory, elucidating the principles and methodology employed by the Muslim jurist in deriving rulings in the field of medical ethics. The four-principles approach, as espoused by Beauchamp and Childress, is also interpreted through the prism of Islamic ethical theory. Each of the four principles (beneficence, nonmaleficence,justice and autonomy) is investigated in turn, looking in particular at the extent to which each is rooted in the Islamic paradigm. This will provide an important insight into Islamic medical ethics, enabling the clinician to have a better informed discussion with the Muslim patient. It will also allow for a higher degree of concordance in consultations and consequently optimise culturally sensitive healthcare delivery.

AllergoOncology: Opposite outcomes of immune tolerance in allergy and cancer.

PubMed

Jensen-Jarolim, E; Bax, H J; Bianchini, R; Crescioli, S; Daniels-Wells, T R; Dombrowicz, D; Fiebiger, E; Gould, H J; Irshad, S; Janda, J; Josephs, D H; Levi-Schaffer, F; O'Mahony, L; Pellizzari, G; Penichet, M L; Redegeld, F; Roth-Walter, F; Singer, J; Untersmayr, E; Vangelista, L; Karagiannis, S N

2018-02-01

While desired for the cure of allergy, regulatory immune cell subsets and nonclassical Th2-biased inflammatory mediators in the tumour microenvironment can contribute to immune suppression and escape of tumours from immunological detection and clearance. A key aim in the cancer field is therefore to design interventions that can break immunological tolerance and halt cancer progression, whereas on the contrary allergen immunotherapy exactly aims to induce tolerance. In this position paper, we review insights on immune tolerance derived from allergy and from cancer inflammation, focusing on what is known about the roles of key immune cells and mediators. We propose that research in the field of AllergoOncology that aims to delineate these immunological mechanisms with juxtaposed clinical consequences in allergy and cancer may point to novel avenues for therapeutic interventions that stand to benefit both disciplines. © 2017 The Authors. Allergy Published by John Wiley & Sons Ltd.

Relationship between Antimalarial Activity and Heme Alkylation for Spiro- and Dispiro-1,2,4-Trioxolane Antimalarials▿

PubMed Central

Creek, Darren J.; Charman, William N.; Chiu, Francis C. K.; Prankerd, Richard J.; Dong, Yuxiang; Vennerstrom, Jonathan L.; Charman, Susan A.

2008-01-01

The reaction of spiro- and dispiro-1,2,4-trioxolane antimalarials with heme has been investigated to provide further insight into the mechanism of action for this important class of antimalarials. A series of trioxolanes with various antimalarial potencies was found to be unreactive in the presence of Fe(III) hemin, but all were rapidly degraded by reduced Fe(II) heme. The major reaction product from the heme-mediated degradation of biologically active trioxolanes was an alkylated heme adduct resulting from addition of a radical intermediate. Under standardized reaction conditions, a correlation (R2 = 0.88) was found between the extent of heme alkylation and in vitro antimalarial activity, suggesting that heme alkylation may be related to the mechanism of action for these trioxolanes. Significantly less heme alkylation was observed for the clinically utilized artemisinin derivatives compared to the equipotent trioxolanes included in this study. PMID:18268087

Mast Cells: Pivotal Players in Cardiovascular Diseases

PubMed Central

Bot, Ilze; van Berkel, Theo J.C; Biessen, Erik A.L

2008-01-01

The clinical outcome of cardiovascular diseases as myocardial infarction and stroke are generally caused by rupture of an atherosclerotic plaque. However, the actual cause of a plaque to rupture is not yet established. Interestingly, pathology studies have shown an increased presence of the mast cell, an important inflammatory effector cell in allergy and host defense, in (peri)vascular tissue during plaque progression, which may point towards a causal role for mast cells. Very recent data in mouse models show that mast cells and derived mediators indeed can profoundly impact plaque progression, plaque stability and acute cardiovascular syndromes such as vascular aneurysm or myocardial infarction. In this review, we discuss recent evidence on the role of mast cells in the progression of cardiovascular disorders and give insight in the therapeutic potential of modulation of mast cell function in these processes to improve the resilience of a plaque to rupture. PMID:19936193

DOE Office of Scientific and Technical Information (OSTI.GOV)

Manglik, Aashish; Kruse, Andrew C.; Kobilka, Tong Sun

Opium is one of the world's oldest drugs, and its derivatives morphine and codeine are among the most used clinical drugs to relieve severe pain. These prototypical opioids produce analgesia as well as many undesirable side effects (sedation, apnoea and dependence) by binding to and activating the G-protein-coupled {mu}-opioid receptor ({mu}-OR) in the central nervous system. Here we describe the 2.8 {angstrom} crystal structure of the mouse {mu}-OR in complex with an irreversible morphinan antagonist. Compared to the buried binding pocket observed in most G-protein-coupled receptors published so far, the morphinan ligand binds deeply within a large solvent-exposed pocket. Ofmore » particular interest, the {mu}-OR crystallizes as a two-fold symmetrical dimer through a four-helix bundle motif formed by transmembrane segments 5 and 6. These high-resolution insights into opioid receptor structure will enable the application of structure-based approaches to develop better drugs for the management of pain and addiction.« less

Integrative biological analysis for neuropsychopharmacology.

PubMed

Emmett, Mark R; Kroes, Roger A; Moskal, Joseph R; Conrad, Charles A; Priebe, Waldemar; Laezza, Fernanda; Meyer-Baese, Anke; Nilsson, Carol L

2014-01-01

Although advances in psychotherapy have been made in recent years, drug discovery for brain diseases such as schizophrenia and mood disorders has stagnated. The need for new biomarkers and validated therapeutic targets in the field of neuropsychopharmacology is widely unmet. The brain is the most complex part of human anatomy from the standpoint of number and types of cells, their interconnections, and circuitry. To better meet patient needs, improved methods to approach brain studies by understanding functional networks that interact with the genome are being developed. The integrated biological approaches--proteomics, transcriptomics, metabolomics, and glycomics--have a strong record in several areas of biomedicine, including neurochemistry and neuro-oncology. Published applications of an integrated approach to projects of neurological, psychiatric, and pharmacological natures are still few but show promise to provide deep biological knowledge derived from cells, animal models, and clinical materials. Future studies that yield insights based on integrated analyses promise to deliver new therapeutic targets and biomarkers for personalized medicine.

An integrated model for the effects of self-reflection and clinical experiential learning on clinical nursing performance in nursing students: A longitudinal study.

PubMed

Pai, Hsiang-Chu

2016-10-01

The use of clinical simulation in undergraduate nursing programs in Taiwan has gradually increased over the past 5years. Previous research has shown that students' experience of anxiety during simulated laboratory sessions influences their self-reflection and learning effectiveness. Thus, further study that tracks what influences students' clinical performance in actual clinical sites is vital. The aim of the study is to develop an integrated model that considers the associations among anxiety, self-reflection, and learning effectiveness and to understand how this model applies to student nurses' clinical performance while on clinical placement. This study used a correlational and longitudinal study design. The 80 nursing students, who ranged in age from 19 to 21 (mean=20.38, SD=0.56), were recruited from a nursing school in southern Taiwan. Data were collected during three phases of implementation using four questionnaires. During the first phase, the State-Trait Anxiety Inventory (STAI), Simulation Learning Effectiveness Scale (SLES), and Self-Reflection and Insight Scale (SRIS) were used after students completed the simulation course in the school simulation laboratory. Nursing students also completed the Holistic Nursing Competence Scale at 2months (Phase 2) and 4months (Phase 3) after clinical practice experience. In Phase 3, students again completed the STAI and SRIS. Partial least squares (PLS), a structural equation modeling (SEM) procedure, was used to test the research model. The findings showed that: (1) at the start of the simulation laboratory, anxiety had a significant negative effect on students' simulation learning effectiveness (SLE; β=-0.14, p<0.05) and on self-reflection with insight (SRI; β=-0.52, p<0.01). Self-reflection also had a significant positive effect on simulation learning effectiveness (β=0.37, p<0.01). Anxiety had a significant negative effect on students' nursing competence during the first 2months of practice in a clinical nursing site (β=-0.20, p<0.01). Simulation learning effectiveness and self-reflection and insight also had a significant positive effect on nursing competence during the first 2months of practice in a clinical site (β=0.13; β=0.16, p<0.05), respectively; and (2) when students practice in a clinical setting, their previous experience of nursing competence during the first 2months of clinical care and their self-reflection and insight have a significant positive effect on their 4-month nursing competence (β=0.58; β=0.27, p<0.01). Anxiety, however, had a negative effect on 4-month nursing competence but not significantly. Overall, 41% of the variance in clinical nursing performance was accounted for by the variables in the integrated model. This study highlights that self-reflection with insight and clinical experience may help students to deflect anxiety that may influence the development of clinical competence. Of note is that real-life clinical experience has a stronger effect on enhancing clinical performance than does a simulation experience. Copyright © 2016 Elsevier Ltd. All rights reserved.

Calculus Students' Understanding of the Vertex of the Quadratic Function in Relation to the Concept of Derivative

ERIC Educational Resources Information Center

Burns-Childers, Annie; Vidakovic, Draga

2018-01-01

The purpose of this study was to gain insight into 30, first year calculus students' understanding of the relationship between the concept of vertex of a quadratic function and the concept of the derivative. APOS (action-process-object-schema) theory was applied as a guiding framework of analysis on student written work, think-aloud and follow up…

Patient-Derived iPSCs and iNs-Shedding New Light on the Cellular Etiology of Neurodegenerative Diseases.

PubMed

Tang, Bor Luen

2018-05-08

Induced pluripotent stem cells (iPSCs) and induced neuronal (iN) cells are very much touted in terms of their potential promises in therapeutics. However, from a more fundamental perspective, iPSCs and iNs are invaluable tools for the postnatal generation of specific diseased cell types from patients, which may offer insights into disease etiology that are otherwise unobtainable with available animal or human proxies. There are two good recent examples of such important insights with diseased neurons derived via either the iPSC or iN approaches. In one, induced motor neurons (iMNs) derived from iPSCs of Amyotrophic lateral sclerosis/Frontotemporal dementia (ALS/FTD) patients with a C9orf72 repeat expansion revealed a haploinsufficiency of protein function resulting from the intronic expansion and deficiencies in motor neuron vesicular trafficking and lysosomal biogenesis that were not previously obvious in knockout mouse models. In another, striatal medium spinal neurons (MSNs) derived directly from fibroblasts of Huntington’s disease (HD) patients recapitulated age-associated disease signatures of mutant Huntingtin (mHTT) aggregation and neurodegeneration that were not prominent in neurons differentiated indirectly via iPSCs from HD patients. These results attest to the tremendous potential for pathologically accurate and mechanistically revealing disease modelling with advances in the derivation of iPSCs and iNs.

Treatment adherence and insight in schizophrenia.

PubMed

Bitter, István; Fehér, László; Tényi, Tamás; Czobor, Pál

2015-01-01

Lack of adherence to treatment in patients with schizophrenia is a major risk factor for poor outcome, including relapse, rehospitalization, and suicide. Poor insight into illness may be a leading cause for partial- or nonadherence since a high proportion of patients with schizophrenia are partially or completely unaware of their mental disorder. The primary objective was to estimate the impact of lack of insight on adherence to medication based on a population of patients in Hungary who had the diagnosis of schizophrenia. The secondary objective was to investigate the association of the different aspects of insight (awareness of illness, the capacity to relabel psychotic experiences as abnormal, treatment acceptance) with (1) recent adherence behavior; (2) current mental state; (3) remission/non-remission status as measured by remission severity criteria; and (4) demographic and treatment history data. This was cross-sectional, noninterventional study, carried out under daily clinical practice conditions, with no influence exerted upon clinical practice in view of the observational nature of the study. Eligibility criteria included: a) patients' age (>18 years), b) diagnosis of schizophrenia (ICD-10), c) signed informed consent, d) no concomitant participation in another clinical trial. Study sites represented Mental Health Centers and outpatient clinics of hospital psychiatric units. Each investigator was asked to enroll patients consecutively. The final analysis sample comprised 262 patients, distributed across 13 sites. The following data were collected: general sociodemographic and clinical data (age, sex, level of education, socioeconomic situation, family support, psychiatric diagnosis, years of evolution, pharmacological and/or psychosocial treatments at the time of inclusion in the study, previous psychiatric admissions), with assessments of the Schedule of Assessing components of Insight (SAI), Compliance Rating Scale (CRS), Clinical Global Impression Scale (CGI-S), Remission Severity Criteria. Patients enrolled in the study had a mean (SD) age of 43.0 (12.6) years, with a 12.3 (3.0) years of education, and approximately evenly balanced gender distribution. According to the clinical judgment of the treating physicians, 29.1% of the patients were not taking their prescribed antipsychotic medication in our target population. The primary logistic regression analysis indicated a significant relationship between the total score on the SAI scale and the Compliance Scale (Spearman correlation=0.58; p<0.0001). The relationship was significant for each of the three subscales of SAI. Secondary analyses showed a significant negative association between compliance and score on the CGI-S scale (Spearman correlation: -0.54; p<0.0001), and compliance and hostility, as measured by the PANSS hostility item (Spearman correlation: -0.40; p<0.0001). We found no significant relationship between compliance and age, gender or education years (p>0.1 in all cases). The results of the present study support the hypothesis that the level of insight and compliance are strongly associated, and that more severe symptoms and increasing levels of hostility, in particular, markedly reduce the compliance of the patients with schizophrenia. Capturing different aspects of insight may be helpful in understanding and improving adherence behavior in clinical practice.

Metacognitive Reflection and Insight Therapy for Early Psychosis: A preliminary study of a novel integrative psychotherapy.

PubMed

Vohs, Jenifer L; Leonhardt, Bethany L; James, Alison V; Francis, Michael M; Breier, Alan; Mehdiyoun, Nikki; Visco, Andrew C; Lysaker, Paul H

2018-05-01

Poor insight impedes treatment in early phase psychosis (EPP). This manuscript outlines preliminary findings of an investigation of the novel metacognitively oriented integrative psychotherapy, Metacognitive Reflection and Insight Therapy, for individuals with early phase psychosis (MERIT-EP). Twenty adults with EPP and poor insight were randomized to either six months of MERIT-EP or treatment as usual (TAU). Therapists were trained and therapy was successfully delivered under routine, outpatient conditions. Insight, assessed before and after treatment, revealed significant improvement for the MERIT-EP, but not TAU, group. These results suggest MERIT-EP is feasible to deliver, accepted by patients, and leads to clinically significant improvements in insight. Copyright © 2017 Elsevier B.V. All rights reserved.

Six-minute walk test and cardiopulmonary exercise testing in patients with chronic heart failure: a comparative analysis on clinical and prognostic insights.

PubMed

Guazzi, Marco; Dickstein, Kenneth; Vicenzi, Marco; Arena, Ross

2009-11-01

The six-minute walk test (6MWT) and cardiopulmonary exercise testing (CPET) are the 2 testing modalities most broadly used for assessing functional limitation in patients with heart failure (HF). A comprehensive comparison on clinical and prognostic validity of the 2 techniques has not been performed and is the aim of the present investigation. Two hundred fifty-three patients diagnosed with systolic (n=211) or diastolic (n=42) HF (age: 61.9+/-10.1 years; New York Heart Association Class: 2.2+/-0.78) underwent a 6MWT and a symptom-limited CPET evaluation and were prospectively followed up. During the 4-year tracking period, there were 43 cardiac-related deaths with an annual cardiac mortality rate of 8.7%. The 6MWT distance correlated with CPET-derived variables (ie, peak Vo(2), Vo(2) at anaerobic threshold, and Ve/Vco(2) slope) and was significantly reduced in proportion with lower peak Vo(2) and higher Ve/Vco(2) slope classes and presence of an exercise oscillatory breathing (EOB) pattern (P<0.01). However, no significant differences were observed in distance covered between survivors and nonsurvivors (353.2+/-95.8 m versus 338.5+/-76.4 m; P=NS). At univariate and multivariate Cox proportional analyses, the association of the 6MWT distance with survival was not significant either as a continuous or dicotomized variable (< or =300 m). Conversely, CPET-derived variables emerged as prognostic with the strongest association found for EOB (systolic HF) and Ve/Vco(2) slope (entire population with HF and patients with a 6MWT< or =300 m). The 6MWT is confirmed to be a simple and reliable first-line test for quantification of exercise intolerance in patients with HF. However, there is no supportive evidence for its use as a prognostic marker in alternative to or in conjunction with CPET-derived variables.

Insight, Neurocognition, and Schizophrenia: Predictive Value of the Wisconsin Card Sorting Test

PubMed Central

Yanos, Philip T.

2013-01-01

Lack of insight in schizophrenia is a key feature of the illness and is associated with both positive and negative clinical outcomes. Previous research supports that neurocognitive dysfunction is related to lack of insight, but studies have not examined how neurocognition relates to change in insight over time. Therefore, the current study sought to understand how performance on the Wisconsin Card Sorting Test (WCST) differed between participants with varying degrees of change in insight over a 6-month period. Fifty-two patients with schizophrenia or schizoaffective disorder were administered the WCST and Positive and Negative Syndrome Scale (PANSS) at baseline, and the PANSS was again administered at a 6-month follow-up assessment. Results indicated that while neurocognition was related to insight at baseline, it was not related to subsequent change in insight. The implications of findings for conceptualization and assessment of insight are discussed. PMID:24303216

Key principles for a national clinical decision support knowledge sharing framework: synthesis of insights from leading subject matter experts.

PubMed

Kawamoto, Kensaku; Hongsermeier, Tonya; Wright, Adam; Lewis, Janet; Bell, Douglas S; Middleton, Blackford

2013-01-01

To identify key principles for establishing a national clinical decision support (CDS) knowledge sharing framework. As part of an initiative by the US Office of the National Coordinator for Health IT (ONC) to establish a framework for national CDS knowledge sharing, key stakeholders were identified. Stakeholders' viewpoints were obtained through surveys and in-depth interviews, and findings and relevant insights were summarized. Based on these insights, key principles were formulated for establishing a national CDS knowledge sharing framework. Nineteen key stakeholders were recruited, including six executives from electronic health record system vendors, seven executives from knowledge content producers, three executives from healthcare provider organizations, and three additional experts in clinical informatics. Based on these stakeholders' insights, five key principles were identified for effectively sharing CDS knowledge nationally. These principles are (1) prioritize and support the creation and maintenance of a national CDS knowledge sharing framework; (2) facilitate the development of high-value content and tooling, preferably in an open-source manner; (3) accelerate the development or licensing of required, pragmatic standards; (4) acknowledge and address medicolegal liability concerns; and (5) establish a self-sustaining business model. Based on the principles identified, a roadmap for national CDS knowledge sharing was developed through the ONC's Advancing CDS initiative. The study findings may serve as a useful guide for ongoing activities by the ONC and others to establish a national framework for sharing CDS knowledge and improving clinical care.

Solving the puzzle of pluripotent stem cell-derived cardiomyocyte maturation: piece by piece.

PubMed

Lundy, David J; Lee, Desy S; Hsieh, Patrick C H

2017-03-01

There is a growing need for in vitro models which can serve as platforms for drug screening and basic research. Human adult cardiomyocytes cannot be readily obtained or cultured, and so pluripotent stem cell-derived cardiomyocytes appear to be an attractive option. Unfortunately, these cells are structurally and functionally immature-more comparable to foetal cardiomyocytes than adult. A recent study by Ruan et al ., provides new insights into accelerating the maturation process and takes us a step closer to solving the puzzle of pluripotent stem cell-derived cardiomyocyte maturation.

Antiprotozoal Nitazoxanide Derivatives: Synthesis, Bioassays and QSAR Study Combined with Docking for Mechanistic Insight

PubMed Central

Scior, Thomas; Lozano-Aponte, Jorge; Ajmani, Subhash; Hernández-Montero, Eduardo; Chávez-Silva, Fabiola; Hernández-Núñez, Emanuel; Moo-Puc, Rosa; Fraguela-Collar, Andres; Navarrete-Vázquez, Gabriel

2015-01-01

In view of the serious health problems concerning infectious diseases in heavily populated areas, we followed the strategy of lead compound diversification to evaluate the near-by chemical space for new organic compounds. To this end, twenty derivatives of nitazoxanide (NTZ) were synthesized and tested for activity against Entamoeba histolytica parasites. To ensure drug-likeliness and activity relatedness of the new compounds, the synthetic work was assisted by a quantitative structure-activity relationships study (QSAR). Many of the inherent downsides – well-known to QSAR practitioners – we circumvented thanks to workarounds which we proposed in prior QSAR publication. To gain further mechanistic insight on a molecular level, ligand-enzyme docking simulations were carried out since NTZ is known to inhibit the protozoal pyruvate ferredoxin oxidoreductase (PFOR) enzyme as its biomolecular target. PMID:25872791

Implementing Peer Learning in Clinical Education: A Framework to Address Challenges In the "Real World".

PubMed

Tai, Joanna Hong Meng; Canny, Benedict J; Haines, Terry P; Molloy, Elizabeth K

2017-01-01

Phenomenon: Peer learning has many benefits and can assist students in gaining the educational skills required in future years when they become teachers themselves. Peer learning may be particularly useful in clinical learning environments, where students report feeling marginalized, overwhelmed, and unsupported. Educational interventions often fail in the workplace environment, as they are often conceived in the "ideal" rather than the complex, messy real world. This work sought to explore barriers and facilitators to implementing peer learning activities in a clinical curriculum. Previous peer learning research results and a matrix of empirically derived peer learning activities were presented to local clinical education experts to generate discussion around the realities of implementing such activities. Potential barriers and limitations of and strategies for implementing peer learning in clinical education were the focus of the individual interviews. Thematic analysis of the data identified three key considerations for real-world implementation of peer learning: culture, epistemic authority, and the primacy of patient-centered care. Strategies for peer learning implementation were also developed from themes within the data, focusing on developing a culture of safety in which peer learning could be undertaken, engaging both educators and students, and establishing expectations for the use of peer learning. Insights: This study identified considerations and strategies for the implementation of peer learning activities, which took into account both educator and student roles. Reported challenges were reflective of those identified within the literature. The resultant framework may aid others in anticipating implementation challenges. Further work is required to test the framework's application in other contexts and its effect on learner outcomes.

The Cancer Genome Atlas Clinical Explorer: a web and mobile interface for identifying clinical-genomic driver associations.

PubMed

Lee, HoJoon; Palm, Jennifer; Grimes, Susan M; Ji, Hanlee P

2015-10-27

The Cancer Genome Atlas (TCGA) project has generated genomic data sets covering over 20 malignancies. These data provide valuable insights into the underlying genetic and genomic basis of cancer. However, exploring the relationship among TCGA genomic results and clinical phenotype remains a challenge, particularly for individuals lacking formal bioinformatics training. Overcoming this hurdle is an important step toward the wider clinical translation of cancer genomic/proteomic data and implementation of precision cancer medicine. Several websites such as the cBio portal or University of California Santa Cruz genome browser make TCGA data accessible but lack interactive features for querying clinically relevant phenotypic associations with cancer drivers. To enable exploration of the clinical-genomic driver associations from TCGA data, we developed the Cancer Genome Atlas Clinical Explorer. The Cancer Genome Atlas Clinical Explorer interface provides a straightforward platform to query TCGA data using one of the following methods: (1) searching for clinically relevant genes, micro RNAs, and proteins by name, cancer types, or clinical parameters; (2) searching for genomic/proteomic profile changes by clinical parameters in a cancer type; or (3) testing two-hit hypotheses. SQL queries run in the background and results are displayed on our portal in an easy-to-navigate interface according to user's input. To derive these associations, we relied on elastic-net estimates of optimal multiple linear regularized regression and clinical parameters in the space of multiple genomic/proteomic features provided by TCGA data. Moreover, we identified and ranked gene/micro RNA/protein predictors of each clinical parameter for each cancer. The robustness of the results was estimated by bootstrapping. Overall, we identify associations of potential clinical relevance among genes/micro RNAs/proteins using our statistical analysis from 25 cancer types and 18 clinical parameters that include clinical stage or smoking history. The Cancer Genome Atlas Clinical Explorer enables the cancer research community and others to explore clinically relevant associations inferred from TCGA data. With its accessible web and mobile interface, users can examine queries and test hypothesis regarding genomic/proteomic alterations across a broad spectrum of malignancies.

A Novel 3D Label-Free Monitoring System of hES-Derived Cardiomyocyte Clusters: A Step Forward to In Vitro Cardiotoxicity Testing

PubMed Central

Jahnke, Heinz-Georg; Steel, Daniella; Fleischer, Stephan; Seidel, Diana; Kurz, Randy; Vinz, Silvia; Dahlenborg, Kerstin; Sartipy, Peter; Robitzki, Andrea A.

2013-01-01

Unexpected adverse effects on the cardiovascular system remain a major challenge in the development of novel active pharmaceutical ingredients (API). To overcome the current limitations of animal-based in vitro and in vivo test systems, stem cell derived human cardiomyocyte clusters (hCMC) offer the opportunity for highly predictable pre-clinical testing. The three-dimensional structure of hCMC appears more representative of tissue milieu than traditional monolayer cell culture. However, there is a lack of long-term, real time monitoring systems for tissue-like cardiac material. To address this issue, we have developed a microcavity array (MCA)-based label-free monitoring system that eliminates the need for critical hCMC adhesion and outgrowth steps. In contrast, feasible field potential derived action potential recording is possible immediately after positioning within the microcavity. Moreover, this approach allows extended observation of adverse effects on hCMC. For the first time, we describe herein the monitoring of hCMC over 35 days while preserving the hCMC structure and electrophysiological characteristics. Furthermore, we demonstrated the sensitive detection and quantification of adverse API effects using E4031, doxorubicin, and noradrenaline directly on unaltered 3D cultures. The MCA system provides multi-parameter analysis capabilities incorporating field potential recording, impedance spectroscopy, and optical read-outs on individual clusters giving a comprehensive insight into induced cellular alterations within a complex cardiac culture over days or even weeks. PMID:23861955

New insights into the electrochemical behavior of acid orange 7: Convergent paired electrochemical synthesis of new aminonaphthol derivatives

NASA Astrophysics Data System (ADS)

Momeni, Shima; Nematollahi, Davood

2017-02-01

Electrochemical behavior of acid orange 7 has been exhaustively studied in aqueous solutions with different pH values, using cyclic voltammetry and constant current coulometry. This study has provided new insights into the mechanistic details, pH dependence and intermediate structure of both electrochemical oxidation and reduction of acid orange 7. Surprisingly, the results indicate that a same redox couple (1-iminonaphthalen-2(1H)-one/1-aminonaphthalen-2-ol) is formed from both oxidation and reduction of acid orange 7. Also, an additional purpose of this work is electrochemical synthesis of three new derivatives of 1-amino-4-(phenylsulfonyl)naphthalen-2-ol (3a-3c) under constant current electrolysis via electrochemical oxidation (and reduction) of acid orange 7 in the presence of arylsulfinic acids as nucleophiles. The results indicate that the electrogenerated 1-iminonaphthalen-2(1 H)-one participates in Michael addition reaction with arylsulfinic acids to form the 1-amino-3-(phenylsulfonyl)naphthalen-2-ol derivatives. The synthesis was carried out in an undivided cell equipped with carbon rods as an anode and cathode.

Praxis induction. Definition, relation to epilepsy syndromes, nosological and prognostic significance. A focused review.

PubMed

Yacubian, Elza Márcia; Wolf, Peter

2014-04-01

There is increasing awareness that reflex epileptic mechanisms provide unique insight into ictogenesis in human epilepsies. Several of the described triggers have in common that they imply complex visuomotor coordination and decision-making; they are today regarded as variations of one principle, i.e. praxis induction (PI). This focused review considers PI from the aspects of history and delineation, clinical and electroencephalographic presentation, syndromatic relations, prevalence, mechanisms of ictogenesis and nosological implications, treatment and prognosis. We reviewed a series of published articles and case reports on PI in order to clarify clinical and electroencephalographic findings, treatment and outcome. Findings of both induction and inhibition by the same stimuli suggest widening the reflex epilepsy concept into a broader one of epilepsies with exogenous modification of ictogenesis. PI is closely related to juvenile myoclonic epilepsy (JME) where hyperexcitability and hyperconnectivity of the entire network of visuomotor coordination seem to provide the precondition for eliciting reflex myocloni in the musculature active in the precipitating task. The conclusions on ictogenesis derived from PI support the concept of JME as a system disorder of the brain. Copyright © 2014 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

Tissue-engineered vascular grafts for use in the treatment of congenital heart disease: from the bench to the clinic and back again.

PubMed

Patterson, Joseph T; Gilliland, Thomas; Maxfield, Mark W; Church, Spencer; Naito, Yuji; Shinoka, Toshiharu; Breuer, Christopher K

2012-05-01

Since the first tissue-engineered vascular graft (TEVG) was implanted in a child over a decade ago, growth in the field of vascular tissue engineering has been driven by clinical demand for improved vascular prostheses with performance and durability similar to an autologous blood vessel. Great strides were made in pediatric congenital heart surgery using the classical tissue engineering paradigm, and cell seeding of scaffolds in vitro remained the cornerstone of neotissue formation. Our second-generation bone marrow cell-seeded TEVG diverged from tissue engineering dogma with a design that induces the recipient to regenerate vascular tissue in situ. New insights suggest that neovessel development is guided by cell signals derived from both seeded cells and host inflammatory cells that infiltrate the graft. The identification of these signals and the regulatory interactions that influence cell migration, phenotype and extracellular matrix deposition during TEVG remodeling are yielding a next-generation TEVG engineered to guide neotissue regeneration without the use of seeded cells. These developments represent steady progress towards our goal of an off-the-shelf tissue-engineered vascular conduit for pediatric congenital heart surgery.

Dynamic microvesicle release and clearance within the cardiovascular system: triggers and mechanisms.

PubMed

Ayers, Lisa; Nieuwland, Rienk; Kohler, Malcolm; Kraenkel, Nicolle; Ferry, Berne; Leeson, Paul

2015-12-01

Interest in cell-derived microvesicles (or microparticles) within cardiovascular diagnostics and therapeutics is rapidly growing. Microvesicles are often measured in the circulation at a single time point. However, it is becoming clear that microvesicle levels both increase and decrease rapidly in response to certain stimuli such as hypoxia, acute cardiac stress, shear stress, hypertriglyceridaemia and inflammation. Consequently, the levels of circulating microvesicles will reflect the balance between dynamic mechanisms for release and clearance. The present review describes the range of triggers currently known to lead to microvesicle release from different cellular origins into the circulation. Specifically, the published data are used to summarize the dynamic impact of these triggers on the degree and rate of microvesicle release. Secondly, a summary of the current understanding of microvesicle clearance via different cellular systems, including the endothelial cell and macrophage, is presented, based on reported studies of clearance in experimental models and clinical scenarios, such as transfusion or cardiac stress. Together, this information can be used to provide insights into potential underlying biological mechanisms that might explain the increases or decreases in circulating microvesicle levels that have been reported and help to design future clinical studies. © 2015 Authors; published by Portland Press Limited.

Drug Insight: mechanisms of action and therapeutic applications for agonists of peroxisome proliferator-activated receptors.

PubMed

Gervois, Philippe; Fruchart, Jean-Charles; Staels, Bart

2007-02-01

Intensive preclinical investigations have delineated a role for peroxisome proliferator-activated receptors (PPARs) in energy metabolism and inflammation. PPARs are activated by natural lipophilic ligands such as fatty acids and their derivatives. Normalization of lipid and glucose metabolism is achieved via pharmacological modulation of PPAR activity. PPARs may also alter atherosclerosis progression through direct effects on the vascular wall. PPARs regulate genes involved in the recruitment of leukocytes to endothelial cells, in vascular inflammation, in macrophage lipid homeostasis, and in thrombosis. PPARs therefore modulate metabolic and inflammatory perturbations that predispose to cardiovascular diseases and type 2 diabetes. The hypolipidemic fibrates and the antidiabetic thiazolidinediones are drugs that act via PPARalpha and PPARgamma, respectively, and are used in clinical practice. PPARbeta/delta ligands are currently in clinical evaluation. The pleiotropic actions of PPARs and the fact that chemically diverse PPAR agonists may induce distinct pharmacological responses have led to the emergence of new concepts for drug design. A more precise understanding of the molecular pathways implicated in the response to chemically distinct PPAR agonists should provide new opportunities for targeted therapeutic applications in the management of the metabolic syndrome, type 2 diabetes, and cardiovascular diseases.

Tissue and Animal Models of Sudden Cardiac Death

PubMed Central

Sallam, Karim; Li, Yingxin; Sager, Philip T.; Houser, Steven R.; Wu, Joseph C.

2015-01-01

Sudden Cardiac Death (SCD) is a common cause of death in patients with structural heart disease, genetic mutations or acquired disorders affecting cardiac ion channels. A wide range of platforms exist to model and study disorders associated with SCD. Human clinical studies are cumbersome and are thwarted by the extent of investigation that can be performed on human subjects. Animal models are limited by their degree of homology to human cardiac electrophysiology including ion channel expression. Most commonly used cellular models are cellular transfection models, which are able to mimic the expression of a single ion channel offering incomplete insight into changes of the action potential profile. Induced pluripotent stem cell derived Cardiomyocytes (iPSC-CMs) resemble, but are not identical, to adult human cardiomyocytes, and provide a new platform for studying arrhythmic disorders leading to SCD. A variety of platforms exist to phenotype cellular models including conventional and automated patch clamp, multi-electrode array, and computational modeling. iPSC-CMs have been used to study Long QT syndrome, catecholaminergic polymorphic ventricular tachycardia, hypertrophic cardiomyopathy and other hereditary cardiac disorders. Although iPSC-CMs are distinct from adult cardiomyocytes, they provide a robust platform to advance the science and clinical care of SCD. PMID:26044252

Brain disorders and the biological role of music.

PubMed

Clark, Camilla N; Downey, Laura E; Warren, Jason D

2015-03-01

Despite its evident universality and high social value, the ultimate biological role of music and its connection to brain disorders remain poorly understood. Recent findings from basic neuroscience have shed fresh light on these old problems. New insights provided by clinical neuroscience concerning the effects of brain disorders promise to be particularly valuable in uncovering the underlying cognitive and neural architecture of music and for assessing candidate accounts of the biological role of music. Here we advance a new model of the biological role of music in human evolution and the link to brain disorders, drawing on diverse lines of evidence derived from comparative ethology, cognitive neuropsychology and neuroimaging studies in the normal and the disordered brain. We propose that music evolved from the call signals of our hominid ancestors as a means mentally to rehearse and predict potentially costly, affectively laden social routines in surrogate, coded, low-cost form: essentially, a mechanism for transforming emotional mental states efficiently and adaptively into social signals. This biological role of music has its legacy today in the disordered processing of music and mental states that characterizes certain developmental and acquired clinical syndromes of brain network disintegration. © The Author (2014). Published by Oxford University Press.

Regulatory dendritic cell therapy: from rodents to clinical application

PubMed Central

Raïch-Regué, Dalia; Glancy, Megan; Thomson, Angus W.

2014-01-01

Dendritic cells (DC) are highly-specialized, bone marrow-derived antigen-presenting cells that induce or regulate innate and adaptive immunity. Regulatory or “tolerogenic” DC play a crucial role in maintaining self tolerance in the healthy steady-state. These regulatory innate immune cells subvert naïve or memory T cell responses by various mechanisms. Regulatory DC (DCreg) also exhibit the ability to induce or restore T cell tolerance in many animal models of autoimmune disease or transplant rejection. There is also evidence that adoptive transfer of DCreg can regulate T cell responses in non-human primates and humans. Important insights gained from in vitro studies and animal models have led recently to the development of clinical grade human DCreg, with potential to treat autoimmune disease or enhance transplant survival while reducing patient dependency on immunosuppressive drugs. Phase I trials have been conducted in type-1 diabetes and rheumatoid arthritis, with results that emphasize the feasibility and safety of DCreg therapy. This mini-review will outline how observations made using animal models have been translated into human use, and discuss the challenges faced in further developing this form of regulatory immune cell therapy in the fields of autoimmunity and transplantation. PMID:24316407

Brain disorders and the biological role of music

PubMed Central

Clark, Camilla N.; Downey, Laura E.

2015-01-01

Despite its evident universality and high social value, the ultimate biological role of music and its connection to brain disorders remain poorly understood. Recent findings from basic neuroscience have shed fresh light on these old problems. New insights provided by clinical neuroscience concerning the effects of brain disorders promise to be particularly valuable in uncovering the underlying cognitive and neural architecture of music and for assessing candidate accounts of the biological role of music. Here we advance a new model of the biological role of music in human evolution and the link to brain disorders, drawing on diverse lines of evidence derived from comparative ethology, cognitive neuropsychology and neuroimaging studies in the normal and the disordered brain. We propose that music evolved from the call signals of our hominid ancestors as a means mentally to rehearse and predict potentially costly, affectively laden social routines in surrogate, coded, low-cost form: essentially, a mechanism for transforming emotional mental states efficiently and adaptively into social signals. This biological role of music has its legacy today in the disordered processing of music and mental states that characterizes certain developmental and acquired clinical syndromes of brain network disintegration. PMID:24847111

NIH Study Offers Insight into Why Cancer Incidence Increases with Age

MedlinePlus

... Record Research & Training Medical Research Initiatives Science Highlights Science Education Research in NIH Labs & Clinics Training Opportunities Library Resources Research Resources Clinical Research Resources Safety, Regulation ...

Hidden benefits of a peer-mentored 'Hospital Orientation Day': first-year medical students' perspectives.

PubMed

Barker, Thomas A; Ngwenya, Nothando; Morley, David; Jones, Ellen; Thomas, Cathryn P; Coleman, Jamie J

2012-01-01

Entering the clinical environment is potentially stressful for junior medical students. We evaluated first-year medical student feedback on a peer-mentored 'Hospital Orientation Day' designed to provide insight into future clinical training. Using a mixed methodology approach data were collected from first-year medical students. Responses to a questionnaire were used to develop a topic guide for focus groups held the next academic year. The questionnaire was completed by 230 first-year students and 32 second years participated in the interviews. Thematic analysis was used to draw conclusions. Analysis of questionnaire responses indicated that students gained insight into future learning. Focus groups then generated five themes: (1) entering the hospital without fear, (2) linking the present with the future, (3) understanding the culture of learning in the clinical years, (4) a 'Backstage Pass' to the clinical world and (5) peer mentors make or break the day. Using peer mentors during the Hospital Orientation Day allowed insight into future learning. We highlight the importance of student Mentors in the success of hospital orientation. To maximise the benefits for first years, we recommend a mentor selection procedure, mentor training opportunities and incentives to optimise mentor performance.

Controllable Syntheses of MOF-Derived Materials.

PubMed

Zou, Kang-Yu; Li, Zuo-Xi

2018-05-02

Metal-organic frameworks (MOFs), as an important kind of porous inorganic-organic hybrid materials with inherent outstanding physicochemistry characteristics, can be widely applied as versatile precursors for the facile preparation of functional MOF-derived materials. However, there are plenty of sophisticated factors during the synthetic process, which is far from reaching the goal of effectively controlling the nature of MOF-derived materials (such as the composition, morphology and surface area). Therefore, it is urgently necessary to develop regular protocols and concepts for controllable syntheses of MOF-derived materials. In this minireview, we mainly summarize and analyze complicated factors in the fabrication of MOF-derived materials according to recently reported literatures, and this provides a new insight into the rational design and syntheses of MOF-derived materials. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Combining Knowledge and Data Driven Insights for Identifying Risk Factors using Electronic Health Records

PubMed Central

Sun, Jimeng; Hu, Jianying; Luo, Dijun; Markatou, Marianthi; Wang, Fei; Edabollahi, Shahram; Steinhubl, Steven E.; Daar, Zahra; Stewart, Walter F.

2012-01-01

Background: The ability to identify the risk factors related to an adverse condition, e.g., heart failures (HF) diagnosis, is very important for improving care quality and reducing cost. Existing approaches for risk factor identification are either knowledge driven (from guidelines or literatures) or data driven (from observational data). No existing method provides a model to effectively combine expert knowledge with data driven insight for risk factor identification. Methods: We present a systematic approach to enhance known knowledge-based risk factors with additional potential risk factors derived from data. The core of our approach is a sparse regression model with regularization terms that correspond to both knowledge and data driven risk factors. Results: The approach is validated using a large dataset containing 4,644 heart failure cases and 45,981 controls. The outpatient electronic health records (EHRs) for these patients include diagnosis, medication, lab results from 2003–2010. We demonstrate that the proposed method can identify complementary risk factors that are not in the existing known factors and can better predict the onset of HF. We quantitatively compare different sets of risk factors in the context of predicting onset of HF using the performance metric, the Area Under the ROC Curve (AUC). The combined risk factors between knowledge and data significantly outperform knowledge-based risk factors alone. Furthermore, those additional risk factors are confirmed to be clinically meaningful by a cardiologist. Conclusion: We present a systematic framework for combining knowledge and data driven insights for risk factor identification. We demonstrate the power of this framework in the context of predicting onset of HF, where our approach can successfully identify intuitive and predictive risk factors beyond a set of known HF risk factors. PMID:23304365

Aerosol absorption measurements and retrievals in shadow2 campaign

NASA Astrophysics Data System (ADS)

Hu, Qiaoyun; Goloub, Philippe; Podvin, Thierry; Veselovskiy, Igor; Lopatin, Anton; Dubovik, Oleg; Torres, Benjamìn; Revilini, Laura; Crumeyrolle, Suzanne; Lapionak, Tatsiana; Deroo, Christine

2018-04-01

Dust, maritime and dust-smoke mixture events observed during SHADOW2 (SaHAran Dust Over West Africa) field campaign are selected and analyzed by using Raman and GARRLiC retrievals. The derived aerosol optical and microphysical properties will be shown. Dust absorption profile and on ground level are derived from GARRLiC retrievals and Aethalometer measurements, respectively. Our results provide a closer insight about dust absorbing properties.

Exploratory study of the association between insight and Theory of Mind (ToM) in stable schizophrenia patients.

PubMed

Pousa, Esther; Duñó, Rosó; Blas Navarro, J; Ruiz, Ada I; Obiols, Jordi E; David, Anthony S

2008-05-01

Poor insight and impairment in Theory of Mind (ToM) reasoning are common in schizophrenia, predicting poorer clinical and functional outcomes. The present study aimed to explore the relationship between these phenomena. 61 individuals with a DSM-IV diagnosis of schizophrenia during a stable phase were included. ToM was assessed using a picture sequencing task developed by Langdon and Coltheart (1999), and insight with the Scale to Assess Unawareness of Mental Disorder (SUMD; Amador et al., 1993). Multivariate linear regression analysis was carried out to estimate the predictive value of insight on ToM, taking into account several possible confounders and interaction variables. No direct significant associations were found between any of the insight dimensions and ToM using bivariate analysis. However, a significant linear regression model which explained 48% of the variance in ToM was revealed in the multivariate analysis. This included the 5 insight dimensions and 3 interaction variables. Misattribution of symptoms--in aware patients with age at onset >20 years--and unawareness of need for medication--in patients with GAF >60--were significantly predictive of better ToM. Insight and ToM are two complex and distinct phenomena in schizophrenia. Relationships between them are mediated by psychosocial, clinical, and neurocognitive variables. Intact ToM may be a prerequisite for aware patients to attribute their symptoms to causes other than mental illness, which could in turn be associated with denial of need for medication.

Selection of and Evidentiary Considerations for Wearable Devices and Their Measurements for Use in Regulatory Decision Making: Recommendations from the ePRO Consortium.

PubMed

Byrom, Bill; Watson, Chris; Doll, Helen; Coons, Stephen Joel; Eremenco, Sonya; Ballinger, Rachel; Mc Carthy, Marie; Crescioni, Mabel; O'Donohoe, Paul; Howry, Cindy

2018-06-01

Wearable devices offer huge potential to collect rich sources of data to provide insights into the effects of treatment interventions. Despite this, at the time of writing this report, limited regulatory guidance on the use of wearables in clinical trial programs has been published. To present recommendations from the Critical Path Institute's Electronic Patient-Reported Outcome Consortium regarding the selection and evaluation of wearable devices and their measurements for use in regulatory trials and to support labeling claims. The evaluation group was composed of Critical Path Institute's clinical outcome assessment (COA) scientists and COA specialists from pharmaceutical trial eCOA solution providers, including COA development and validation specialists. The resulting recommendations were drawn from a broad range of backgrounds, perspectives, and expertise that enriched the development of this report. Recommendations were developed through analysis of existing regulatory guidance relating to COA development and use in clinical trials, medical device certification/clearance regulations, literature-reported best practice, and practical experience of wearable technology application in clinical trials. We identify the essential properties of fit-for-purpose wearables and propose evidence needed to support their use. In addition, we overview the activities required to establish clinical endpoints derived from wearables data. Using this framework, we believe there is enough current understanding to promote the appropriate use of wearables in study protocols. We hope this will provide a basis for discussion among clinical trial stakeholders and catalyze the development of more robust regulatory guidance. Copyright © 2018 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Key factors of clinical research network capacity building.

PubMed

Li, Guowei; Wu, Qianyu; Jin, Yanling; Vanniyasingam, Thuva; Thabane, Lehana

2018-01-01

In general, clinical research network capacity building refers to programs aimed at enhancing networks of researchers to conduct clinical research. Although in the literature there is a large body of research on how to develop and build capacity in clinical research networks, the conceptualizations and implementations remain controversial and challenging. Moreover, the experiences learnt from the past accomplishments and failures can assist in the future capacity building efforts to be more practical, effective and efficient. In this paper, we aim to provide an overview of capacity building in clinical research network by (1) identifying the key barriers to clinical research network capacity building, (2) providing insights into how to overcome those obstacles, and (3) sharing our experiences in collaborating with national and international partners to build capacity in clinical research networks. In conclusion, we have provided some insight into how to address the key factors of clinical research network capacity building and shared some empirical experiences. A successful capacity building practice requires a joint endeavor to procure sufficient resources and support from the relevant stakeholders, to ensure its efficiency, cost-effectiveness, and sustainability.

Why might people donate tissue for cancer research? Insights from organ/tissue/blood donation and clinical research.

PubMed

Axler, Renata E; Irvine, Rob; Lipworth, Wendy; Morrell, Bronwen; Kerridge, Ian H

2008-01-01

Little is known about why patients with cancer do or do not donate their biopsied/cancerous tissue to research. A review of the literature on motivations to participate in clinical research and to donate tissues/organs for therapeutic use may provide some insights relevant to tumour banking research. While more research is necessary, a better understanding of the factors that motivate patients to give or refuse consent to tumour banking may ultimately improve consent practices, public trust and donation rates. Copyright 2008 S. Karger AG, Basel.

Hypnosis in palliative care: from clinical insights to the science of self-regulation.

PubMed

Landry, Mathieu; Stendel, Moriah; Landry, Michel; Raz, Amir

2018-01-01

Palliative care spans a wide-ranging spectrum: from pain-management to spiritual support. As the demand for end-of-life care increases, so does the demand for innovative, effective, interventions. Mind-body techniques seem especially advantageous in a palliative context. Here we show that hypnosis serves an excellent adjunct therapy in palliative care to boost the efficacy of standard treatments. With the overarching goal of bridging clinical and scientific insights, we outline how five core principles of hypnosis can benefit the diverse needs of palliative care.

Immunosuppressive Mesenchymal Stromal Cells Derived from Human-Induced Pluripotent Stem Cells Induce Human Regulatory T Cells In Vitro and In Vivo

PubMed Central

Roux, Clémence; Saviane, Gaëlle; Pini, Jonathan; Belaïd, Nourhène; Dhib, Gihen; Voha, Christine; Ibáñez, Lidia; Boutin, Antoine; Mazure, Nathalie M.; Wakkach, Abdelilah; Blin-Wakkach, Claudine; Rouleau, Matthieu

2018-01-01

Despite mesenchymal stromal cells (MSCs) are considered as a promising source of cells to modulate immune functions on cells from innate and adaptive immune systems, their clinical use remains restricted (few number, limited in vitro expansion, absence of a full phenotypic characterization, few insights on their in vivo fate). Standardized MSCs derived in vitro from human-induced pluripotent stem (huIPS) cells, remediating part of these issues, are considered as well as a valuable tool for therapeutic approaches, but their functions remained to be fully characterized. We generated multipotent MSCs derived from huiPS cells (huiPS-MSCs), and focusing on their immunosuppressive activity, we showed that human T-cell activation in coculture with huiPS-MSCs was significantly reduced. We also observed the generation of functional CD4+ FoxP3+ regulatory T (Treg) cells. Further tested in vivo in a model of human T-cell expansion in immune-deficient NSG mice, huiPS-MSCs immunosuppressive activity prevented the circulation and the accumulation of activated human T cells. Intracytoplasmic labeling of cytokines produced by the recovered T cells showed reduced percentages of human-differentiated T cells producing Th1 inflammatory cytokines. By contrast, T cells producing IL-10 and FoxP3+-Treg cells, absent in non-treated animals, were detected in huiPS-MSCs treated mice. For the first time, these results highlight the immunosuppressive activity of the huiPS-MSCs on human T-cell stimulation with a concomitant generation of human Treg cells in vivo. They may favor the development of new tools and strategies based on the use of huiPS cells and their derivatives for the induction of immune tolerance. PMID:29422893

Immunosuppressive Mesenchymal Stromal Cells Derived from Human-Induced Pluripotent Stem Cells Induce Human Regulatory T Cells In Vitro and In Vivo.

PubMed

Roux, Clémence; Saviane, Gaëlle; Pini, Jonathan; Belaïd, Nourhène; Dhib, Gihen; Voha, Christine; Ibáñez, Lidia; Boutin, Antoine; Mazure, Nathalie M; Wakkach, Abdelilah; Blin-Wakkach, Claudine; Rouleau, Matthieu

2017-01-01

Despite mesenchymal stromal cells (MSCs) are considered as a promising source of cells to modulate immune functions on cells from innate and adaptive immune systems, their clinical use remains restricted (few number, limited in vitro expansion, absence of a full phenotypic characterization, few insights on their in vivo fate). Standardized MSCs derived in vitro from human-induced pluripotent stem (huIPS) cells, remediating part of these issues, are considered as well as a valuable tool for therapeutic approaches, but their functions remained to be fully characterized. We generated multipotent MSCs derived from huiPS cells (huiPS-MSCs), and focusing on their immunosuppressive activity, we showed that human T-cell activation in coculture with huiPS-MSCs was significantly reduced. We also observed the generation of functional CD4 + FoxP3 + regulatory T (Treg) cells. Further tested in vivo in a model of human T-cell expansion in immune-deficient NSG mice, huiPS-MSCs immunosuppressive activity prevented the circulation and the accumulation of activated human T cells. Intracytoplasmic labeling of cytokines produced by the recovered T cells showed reduced percentages of human-differentiated T cells producing Th1 inflammatory cytokines. By contrast, T cells producing IL-10 and FoxP3 + -Treg cells, absent in non-treated animals, were detected in huiPS-MSCs treated mice. For the first time, these results highlight the immunosuppressive activity of the huiPS-MSCs on human T-cell stimulation with a concomitant generation of human Treg cells in vivo . They may favor the development of new tools and strategies based on the use of huiPS cells and their derivatives for the induction of immune tolerance.

Students' Assessment and Self-assessment of Nursing Clinical Faculty Competencies: Important Feedback in Clinical Education?

PubMed

Lovrić, Robert; Prlić, Nada; Zec, Davor; Pušeljić, Silvija; Žvanut, Boštjan

2015-01-01

The students' assessment of clinical faculty competencies and the faculty members' self-assessment can provide important information about nursing clinical education. The aim of this study was to identify the differences between the students' assessment of the clinical faculty member's competencies and the faculty member's self-assessment. These differences can reveal interesting insights relevant for improving clinical practice.

Video observation in HIT development: lessons learned on benefits and challenges.

PubMed

Høstgaard, Anna Marie; Bertelsen, Pernille

2012-08-22

Experience shows that the precondition for the development of successful health information technologies is a thorough insight into clinical work practice. In contemporary clinical work practice, clinical work and health information technology are integrated, and part of the practice is tacit. When work practice becomes routine, it slips to the background of the conscious awareness and becomes difficult to recognize without the context to support recall. This means that it is difficult to capture with traditional ethnographic research methods or in usability laboratories or clinical set ups. Observation by the use of the video technique within healthcare settings has proven to be capable of providing a thorough insight into the complex clinical work practice and its context - including parts of the tacit practice. The objective of this paper is 1) to argue for the video observation technique to inform and improve health-information-technology development and 2) to share insights and lessons learned on benefits and challenges when using the video observation technique within healthcare settings. A multiple case study including nine case studies conducted by DaCHI researchers 2004-2011 using audio-visual, non-participant video observation for data collection within different healthcare settings. In HIT development, video observation is beneficial for 1) informing and improving system design 2) studying changes in work practice 3) identifying new potentials and 4) documenting current work practices. The video observation technique used within healthcare settings is superior to other ethnographic research methods when it comes to disclosing the complexity in clinical work practice. The insights gained are far more realistic compared to traditional ethnographic studies or usability studies and studies in clinical set ups. Besides, the data generated through video recordings provide a solid basis for dialog between the health care professionals involved. The most important lessons learned are that a well considered methodology and clear formulated objectives are imperative, in order to stay focused during the data rich analysis phase. Additionally, the video observation technique is primarily recommended for studies of specific clinical work practices within delimited clinical settings. Overall, the video observation technique has proven to be capable of improving our understanding of the interwoven relation between clinical work practice and HIT and to inform us about user requirements and needs for HIT, which is a precondition for the development of more successful HIT systems in the future.

Spread of Vaccine-Derived Poliovirus from a Paralytic Case in an Immunodeficient Child: an Insight into the Natural Evolution of Oral Polio Vaccine

PubMed Central

Cherkasova, E. A.; Yakovenko, M. L.; Rezapkin, G. V.; Korotkova, E. A.; Ivanova, O. E.; Eremeeva, T. P.; Krasnoproshina, L. I.; Romanenkova, N. I.; Rozaeva, N. R.; Sirota, L.; Agol, V. I.; Chumakov, K. M.

2005-01-01

Sabin strains used in the manufacture of oral polio vaccine (OPV) replicate in the human organism and can give rise to vaccine-derived polioviruses. The increased neurovirulence of vaccine derivatives has been known since the beginning of OPV use, but their ability to establish circulation in communities has been recognized only recently during the latest stages of the polio eradication campaign. This important observation called for studies of their emergence and evolution as well as extensive surveillance to determine the scope of this phenomenon. Here, we present the results of a study of vaccine-derived isolates from an immunocompromised poliomyelitis patient, the contacts, and the local sewage. All isolates were identified as closely related and slightly evolved vaccine derivatives with a recombinant type 2/type 1 genome. The strains also shared several amino acid substitutions including a mutation in the VP1 protein that was previously shown to be associated with the loss of attenuation. Another mutation in the VP3 protein resulted in altered immunological properties of the isolates, possibly facilitating virus spread in immunized populations. The patterns and rates of the accumulation of synonymous mutations in isolates collected from the patient over the extended period of excretion suggest either a substantially nonuniform rate of mutagenesis throughout the genome, or, more likely, the strains may have been intratypic recombinants between coevolving derivatives with different degrees of divergence from the vaccine parent. This study provides insight into the early stages of the establishment of circulation by runaway vaccine strains. PMID:15613335

Sweat glucose and GLUT2 expression in atopic dermatitis: Implication for clinical manifestation and treatment

PubMed Central

Ono, Emi; Mori, Yuki; Yoshioka, Yoshichika; Nomura, Yuko; Munetsugu, Takichi; Yokozeki, Hiroo; Katayama, Ichiro

2018-01-01

Sweat includes active components and metabolites, which are needed to maintain skin homeostasis. Component changes in sweat derived from atopic dermatitis (AD) have been reported. To investigate the influence of sweat components on the pathogenesis of AD, we performed a multifaceted assessment, including nuclear magnetic resonance spectroscopy-based metabolomic analysis, and linked these features to clinical features of AD. Distinctive properties of AD sweat are the quite-variation in protein, anti-microbial peptides and glucose concentrations. pH, sodium, and other salt levels in sweat of AD were comparable to that of healthy subjects. Sweat from AD patients with acute inflammation had a more prominent increase in glucose concentration than sweat from healthy individuals or those with AD with chronic inflammation. Topical glucose application delayed recovery of transepidermal water loss in barrier-disrupted mice. Furthermore, the glucose transporter GLUT2 was highly expressed in the lumen of sweat glands from AD patients. AD patients with chronic inflammation had significantly increased GLUT2 mRNA expression and near normal sweat glucose levels. Despite the small sample size in our study, we speculate that the increased glucose levels might be affected by AD severity and phenotype. We hope that this report will bring novel insight into the impact of sweat components on the clinical manifestation of AD. PMID:29677207

Culture on 3D Chitosan-Hyaluronic Acid Scaffolds Enhances Stem Cell Marker Expression and Drug Resistance in Human Glioblastoma Cancer Stem Cells.

PubMed

Wang, Kui; Kievit, Forrest M; Erickson, Ariane E; Silber, John R; Ellenbogen, Richard G; Zhang, Miqin

2016-12-01

The lack of in vitro models that support the growth of glioblastoma (GBM) stem cells (GSCs) that underlie clinical aggressiveness hinders developing new, effective therapies for GBM. While orthotopic patient-derived xenograft models of GBM best reflect in vivo tumor behavior, establishing xenografts is a time consuming, costly, and frequently unsuccessful endeavor. To address these limitations, a 3D porous scaffold composed of chitosan and hyaluronic acid (CHA) is synthesized. Growth and expression of the cancer stem cell (CSC) phenotype of the GSC GBM6 taken directly from fresh xenogratfs grown on scaffolds or as adherent monolayers is compared. While 2D adherent cultures grow as monolayers of flat epitheliod cells, GBM6 cells proliferate within pores of CHA scaffolds as clusters of self-adherent ovoid cells. Growth on scaffolds is accompanied by greater expression of genes that mediate epithelial-mesenchymal transition and maintain a primitive, undifferentiated phenotype, hallmarks of CSCs. Scaffold-grown cells also display higher expression of genes that promote resistance to hypoxia-induced oxidative stress. In accord, scaffold-grown cells show markedly greater resistance to clinically utilized alkylating agents compared to adherent cells. These findings suggest that our CHA scaffolds better mimic in vivo biological and clinical behavior and provide insights for developing novel individualized treatments. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Insights into the pathogenesis of GvHD: what mice can teach us about man.

PubMed

Hülsdünker, J; Zeiser, R

2015-01-01

Acute graft-vs-host disease (GvHD) is a life-threatening complication of allogeneic hematopoietic cell transplantation (allo-HCT). Most of the knowledge about the biology of GvHD is derived from mouse models of this disease and therefore a critical analysis of potential advantages and disadvantages of the murine GvHD models is important to classify and understand the findings made in these models. The central events leading up to GvHD were characterized in three phases which includes the tissue damage-phase, the T cell priming-phase and the effector-phase, when the disease becomes clinically overt. The role of individual cytokines, chemokines, transcription factor or receptors was studied in these models by using gene deficient or transgenic mice in the donor or recipient compartments. Besides, numerous studies have been performed in these models to prevent or treat GvHD. Several recent clinical trials were all based on previously reported findings from the mouse model of GvHD such as the trials on CCR5-blockade, donor statin treatment, vorinostat treatment or adoptive transfer of regulatory T cells for GvHD prevention. The different mouse models for GvHD and graft-vs-leukemia effects are critically reviewed and their impact on current clinical practice is discussed. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Variability in Cortical Representations of Speech Sound Perception

ERIC Educational Resources Information Center

Boatman, Dana F.

2007-01-01

Recent brain mapping studies have provided new insights into the cortical systems that mediate human speech perception. Electrocortical stimulation mapping (ESM) is a brain mapping method that is used clinically to localize cortical functions in neurosurgical patients. Recent ESM studies have yielded new insights into the cortical systems that…

Computational Modeling of Inflammation and Wound Healing

PubMed Central

Ziraldo, Cordelia; Mi, Qi; An, Gary; Vodovotz, Yoram

2013-01-01

Objective Inflammation is both central to proper wound healing and a key driver of chronic tissue injury via a positive-feedback loop incited by incidental cell damage. We seek to derive actionable insights into the role of inflammation in wound healing in order to improve outcomes for individual patients. Approach To date, dynamic computational models have been used to study the time evolution of inflammation in wound healing. Emerging clinical data on histo-pathological and macroscopic images of evolving wounds, as well as noninvasive measures of blood flow, suggested the need for tissue-realistic, agent-based, and hybrid mechanistic computational simulations of inflammation and wound healing. Innovation We developed a computational modeling system, Simple Platform for Agent-based Representation of Knowledge, to facilitate the construction of tissue-realistic models. Results A hybrid equation–agent-based model (ABM) of pressure ulcer formation in both spinal cord-injured and -uninjured patients was used to identify control points that reduce stress caused by tissue ischemia/reperfusion. An ABM of arterial restenosis revealed new dynamics of cell migration during neointimal hyperplasia that match histological features, but contradict the currently prevailing mechanistic hypothesis. ABMs of vocal fold inflammation were used to predict inflammatory trajectories in individuals, possibly allowing for personalized treatment. Conclusions The intertwined inflammatory and wound healing responses can be modeled computationally to make predictions in individuals, simulate therapies, and gain mechanistic insights. PMID:24527362

Passive Immunoprophylaxis for the Protection of the Mother and Her Baby: Insights from In Vivo Models of Antibody Transport

PubMed Central

Xu, Yanqun; Mahmood, Iftekhar; Zhong, Lilin; Zhang, Pei

2017-01-01

Pregnant women are at high risk for infection by pathogens. Vertical transmission of infectious agents, such as Zika, hepatitis B, and cytomegalovirus during pregnancy, remains a public health problem, associated with dire outcomes for the neonate. Thus, a safe prophylactic and therapeutic approach for protecting the mother and the neonate from infections remains a high priority. Our work is focused on better understanding the safety and efficacy determinants of IgG antibody preparations when used during pregnancy to benefit the mother and her baby. Using pregnant guinea pigs, we demonstrated that biodistribution of administered IgG to the fetus increases with gestation and results in lower maternal and higher fetal antibody concentrations as pregnancy progresses. Data suggests that partition of antibody immunotherapy to the fetal compartment may contribute to a lower maternal exposure (as measured by the AUC) and a shorter mean residence time of the IgG therapeutic at the end of pregnancy compared to nonpregnant age-matched controls, irrespective of the administered dose. Our studies provide insights on the importance of selecting an efficacious dose in pregnancy that takes into account IgG biodistribution to the fetus. The use of appropriate animal models of placental transfer and infectious disease during pregnancy would facilitate pharmacokinetic modeling to derive a starting dose in clinical trials. PMID:28168206

Cognitive deficits and reduced insight in primary progressive aphasia.

PubMed

Banks, Sarah Jane; Weintraub, Sandra

2008-01-01

Primary progressive aphasia (PPA) is a form of dementia caused by frontotemporal lobar degeneration. Unlike aphasia due to stroke, in which the association between particular aphasia profiles and insight has been well characterized, this relationship has not been investigated in PPA. Reduced insight is seen in other neurological conditions, but tends to involve right hemisphere damage, whereas PPA is predominantly a left hemisphere disorder. The aim of the current study was to examine whether fluent aphasia with less meaningful speech output, associated with diminished insight in stroke, is also characteristic of PPA patients with reduced insight. Fourteen PPA patients were studied. Results indicated that reduced information content in speech and poor performance on a nonlanguage test, the Pyramids and Palm Trees test, predicted reduced insight. This study has implications for the anatomical network involved in insight and clinical implications in terms of selecting interventions appropriate for individual patients with PPA.

Correlations Between Awareness of Illness (Insight) and History of Addiction in Heroin-Addicted Patients

PubMed Central

Maremmani, Angelo Giovanni Icro; Rovai, Luca; Rugani, Fabio; Pacini, Matteo; Lamanna, Francesco; Bacciardi, Silvia; Perugi, Giulio; Deltito, Joseph; Dell’Osso, Liliana; Maremmani, Icro

2012-01-01

In a group of 1066 heroin addicts, who were seeking treatment for opioid agonist treatment, we looked for differences in historical, demographic, and clinical characteristics, between patients with different levels of awareness of illness (insight). The results showed that, in the cohort studied, a majority of subjects lacked insight into their heroin-use behavior. Compared with the impaired-insight group, those who possessed insight into their illness showed significantly greater awareness of past social, somatic, and psychopathological impairments, and had a greater number of past treatment-seeking events for heroin addiction. In contrast with other psychiatric illnesses, the presence of awareness appears to be related to the passing of time and to the worsening of the illness. Methodologies to improve the insight of patients should, therefore, be targeted more directly on patients early in their history of heroin dependence, because the risk of lack of insight is greatest during this period. PMID:22787450

Cognitive Deficits and Reduced Insight in Primary Progressive Aphasia

PubMed Central

Banks, Sarah Jane; Weintraub, Sandra

2009-01-01

Primary progressive aphasia (PPA) is a form of dementia caused by frontotemporal lobar degeneration. Unlike aphasia due to stroke, in which the association between particular aphasia profiles and insight has been well characterized, this relationship has not been investigated in PPA. Reduced insight is seen in other neurological conditions, but tends to involve right hemisphere damage, whereas PPA is predominantly a left hemisphere disorder. The aim of the current study was to examine whether fluent aphasia with less meaningful speech output, associated with diminished insight in stroke, is also characteristic of PPA patients with reduced insight. Fourteen PPA patients were studied. Results indicated that reduced information content in speech and poor performance on a nonlanguage test, the Pyramids and Palm Trees test, predicted reduced insight. This study has implications for the anatomical network involved in insight and clinical implications in terms of selecting interventions appropriate for individual patients with PPA. PMID:18836134

Echocardiography Practice: Insights into Appropriate Clinical Use, Technical Competence and Quality Improvement Program

PubMed Central

Kossaify, Antoine; Grollier, Gilles

2014-01-01

Echocardiography accounts for nearly half of all cardiac imaging techniques. It is a widely available and adaptable tool, as well as being a cost-effective and mainly a non-invasive test. In addition, echocardiography provides extensive clinical data, which is related to the presence or advent of different modalities (tissue Doppler imaging, speckle tracking imaging, three-dimensional mode, contrast echo, etc.), different approaches (transesophageal, intravascular, etc.), and different applications (ie, heart failure/resynchronization studies, ischemia/stress echo, etc.). In view of this, it is essential to conform to criteria of appropriate use and to keep standards of competence. In this study, we sought to review and discuss clinical practice of echocardiography in light of the criteria of appropriate clinical use, also we present an insight into echocardiographic technical competence and quality improvement project. PMID:24516342

A human neurodevelopmental model for Williams syndrome.

PubMed

Chailangkarn, Thanathom; Trujillo, Cleber A; Freitas, Beatriz C; Hrvoj-Mihic, Branka; Herai, Roberto H; Yu, Diana X; Brown, Timothy T; Marchetto, Maria C; Bardy, Cedric; McHenry, Lauren; Stefanacci, Lisa; Järvinen, Anna; Searcy, Yvonne M; DeWitt, Michelle; Wong, Wenny; Lai, Philip; Ard, M Colin; Hanson, Kari L; Romero, Sarah; Jacobs, Bob; Dale, Anders M; Dai, Li; Korenberg, Julie R; Gage, Fred H; Bellugi, Ursula; Halgren, Eric; Semendeferi, Katerina; Muotri, Alysson R

2016-08-18

Williams syndrome is a genetic neurodevelopmental disorder characterized by an uncommon hypersociability and a mosaic of retained and compromised linguistic and cognitive abilities. Nearly all clinically diagnosed individuals with Williams syndrome lack precisely the same set of genes, with breakpoints in chromosome band 7q11.23 (refs 1-5). The contribution of specific genes to the neuroanatomical and functional alterations, leading to behavioural pathologies in humans, remains largely unexplored. Here we investigate neural progenitor cells and cortical neurons derived from Williams syndrome and typically developing induced pluripotent stem cells. Neural progenitor cells in Williams syndrome have an increased doubling time and apoptosis compared with typically developing neural progenitor cells. Using an individual with atypical Williams syndrome, we narrowed this cellular phenotype to a single gene candidate, frizzled 9 (FZD9). At the neuronal stage, layer V/VI cortical neurons derived from Williams syndrome were characterized by longer total dendrites, increased numbers of spines and synapses, aberrant calcium oscillation and altered network connectivity. Morphometric alterations observed in neurons from Williams syndrome were validated after Golgi staining of post-mortem layer V/VI cortical neurons. This model of human induced pluripotent stem cells fills the current knowledge gap in the cellular biology of Williams syndrome and could lead to further insights into the molecular mechanism underlying the disorder and the human social brain.

A human neurodevelopmental model for Williams syndrome

PubMed Central

Chailangkarn, Thanathom; Trujillo, Cleber A.; Freitas, Beatriz C.; Hrvoj-Mihic, Branka; Herai, Roberto H.; Yu, Diana X.; Brown, Timothy T.; Marchetto, Maria C. N.; Bardy, Cedric; McHenry, Lauren; Stefanacci, Lisa; Järvinen, Anna; Searcy, Yvonne M.; DeWitt, Michelle; Wong, Wenny; Lai, Philip; Ard, M. Colin; Hanson, Kari L.; Romero, Sarah; Jacobs, Bob; Dale, Anders M.; Dai, Li; Korenberg, Julie R.; Gage, Fred H.; Bellugi, Ursula; Halgren, Eric; Semendeferi, Katerina; Muotri, Alysson R.

2016-01-01

Summary Williams syndrome (WS) is a genetic neurodevelopmental disorder characterized by an uncommon hypersociability and a mosaic of retained and compromised linguistic and cognitive abilities. Nearly all clinically diagnosed individuals with WS lack precisely the same set of genes, with breakpoints in chromosome band 7q11.231–5. The contribution of specific genes to the neuroanatomical and functional alterations, leading to behavioral pathologies in humans, remains largely unexplored. Here, we investigate neural progenitor cells (NPCs) and cortical neurons derived from WS and typically developing (TD) induced pluripotent stem cells (iPSCs). WS NPCs have an increased doubling time and apoptosis compared to TD NPCs. Using an atypical WS subject6, 7, we narrowed this cellular phenotype to a single gene candidate, FZD9. At the neuronal stage, WS-derived layers V/VI cortical neurons were characterized by longer total dendrites, increased numbers of spines and synapses, aberrant calcium oscillation and altered network connectivity. Morphometric alterations observed in WS neurons were validated after Golgi staining of postmortem layers V/VI cortical neurons. This human iPSC model8 fills in the current knowledge gap in WS cellular biology and could lead to further insights into the molecular mechanism underlying the disorder and the human social brain. PMID:27509850

Variance analysis of x-ray CT sinograms in the presence of electronic noise background.

PubMed

Ma, Jianhua; Liang, Zhengrong; Fan, Yi; Liu, Yan; Huang, Jing; Chen, Wufan; Lu, Hongbing

2012-07-01

Low-dose x-ray computed tomography (CT) is clinically desired. Accurate noise modeling is a fundamental issue for low-dose CT image reconstruction via statistics-based sinogram restoration or statistical iterative image reconstruction. In this paper, the authors analyzed the statistical moments of low-dose CT data in the presence of electronic noise background. The authors first studied the statistical moment properties of detected signals in CT transmission domain, where the noise of detected signals is considered as quanta fluctuation upon electronic noise background. Then the authors derived, via the Taylor expansion, a new formula for the mean-variance relationship of the detected signals in CT sinogram domain, wherein the image formation becomes a linear operation between the sinogram data and the unknown image, rather than a nonlinear operation in the CT transmission domain. To get insight into the derived new formula by experiments, an anthropomorphic torso phantom was scanned repeatedly by a commercial CT scanner at five different mAs levels from 100 down to 17. The results demonstrated that the electronic noise background is significant when low-mAs (or low-dose) scan is performed. The influence of the electronic noise background should be considered in low-dose CT imaging.

Variance analysis of x-ray CT sinograms in the presence of electronic noise background

PubMed Central

Ma, Jianhua; Liang, Zhengrong; Fan, Yi; Liu, Yan; Huang, Jing; Chen, Wufan; Lu, Hongbing

2012-01-01

Purpose: Low-dose x-ray computed tomography (CT) is clinically desired. Accurate noise modeling is a fundamental issue for low-dose CT image reconstruction via statistics-based sinogram restoration or statistical iterative image reconstruction. In this paper, the authors analyzed the statistical moments of low-dose CT data in the presence of electronic noise background. Methods: The authors first studied the statistical moment properties of detected signals in CT transmission domain, where the noise of detected signals is considered as quanta fluctuation upon electronic noise background. Then the authors derived, via the Taylor expansion, a new formula for the mean–variance relationship of the detected signals in CT sinogram domain, wherein the image formation becomes a linear operation between the sinogram data and the unknown image, rather than a nonlinear operation in the CT transmission domain. To get insight into the derived new formula by experiments, an anthropomorphic torso phantom was scanned repeatedly by a commercial CT scanner at five different mAs levels from 100 down to 17. Results: The results demonstrated that the electronic noise background is significant when low-mAs (or low-dose) scan is performed. Conclusions: The influence of the electronic noise background should be considered in low-dose CT imaging. PMID:22830738

Taxane-mediated radiosensitization derives from chromosomal missegregation on tripolar mitotic spindles orchestrated by AURKA and TPX2.

PubMed

Orth, M; Unger, K; Schoetz, U; Belka, C; Lauber, K

2018-01-04

Taxane-based radiochemotherapy is a central treatment option for various cancer entities in locally advanced stages. The therapeutic synergism of this combined modality approach due to taxane-mediated radiosensitization of cancer cells is well-known. However, the underlying molecular mechanisms remain largely elusive, and mechanism-derived predictive markers of taxane-based radiochemotherapy are currently not available. Here, we show that clinically relevant doses of Paclitaxel, the prototype taxane, stimulate a tripolar mode of mitosis leading to chromosomal missegregation and aneuploidization rather than interfering with cell cycle progression. This distinct mitotic phenotype was interlinked with Paclitaxel-mediated radiosensitization via overexpression of mitotic Aurora kinase A (AURKA) and its cofactor TPX2 whose knockdown rescued the bipolar mode of cell division and largely attenuated the radiosensitizing effects of Paclitaxel. In the cancer genome atlas (TCGA) lung adenocarcinoma cohort, high expression levels of AURKA and TPX2 were associated with specifically improved overall survival upon taxane-based radiochemotherapy, but not in case of non-taxane-based radiochemotherapy, chemo- or radiotherapy only. Thus, our data provide insights into Paclitaxel-mediated radiosensitization on a mechanistic and molecular level and identify AURKA and TPX2 as the first potential mechanism-based, predictive markers of taxane-based radiochemotherapy.

Tunable Surface Repellency Maintains Stemness and Redox Capacity of Human Mesenchymal Stem Cells.

PubMed

Balikov, Daniel A; Crowder, Spencer W; Boire, Timothy C; Lee, Jung Bok; Gupta, Mukesh K; Fenix, Aidan M; Lewis, Holley N; Ambrose, Caitlyn M; Short, Philip A; Kim, Chang Soo; Burnette, Dylan T; Reilly, Matthew A; Murthy, N Sanjeeva; Kang, Mi-Lan; Kim, Won Shik; Sung, Hak-Joon

2017-07-12

Human bone marrow derived mesenchymal stem cells (hMSCs) hold great promise for regenerative medicine due to their multipotent differentiation capacity and immunomodulatory capabilities. Substantial research has elucidated mechanisms by which extracellular cues regulate hMSC fate decisions, but considerably less work has addressed how material properties can be leveraged to maintain undifferentiated stem cells. Here, we show that synthetic culture substrates designed to exhibit moderate cell-repellency promote high stemness and low oxidative stress-two indicators of naïve, healthy stem cells-in commercial and patient-derived hMSCs. Furthermore, the material-mediated effect on cell behavior can be tuned by altering the molar percentage (mol %) and/or chain length of poly(ethylene glycol) (PEG), the repellant block linked to hydrophobic poly(ε-caprolactone) (PCL) in the copolymer backbone. Nano- and angstrom-scale characterization of the cell-material interface reveals that PEG interrupts the adhesive PCL domains in a chain-length-dependent manner; this prevents hMSCs from forming mature focal adhesions and subsequently promotes cell-cell adhesions that require connexin-43. This study is the first to demonstrate that intrinsic properties of synthetic materials can be tuned to regulate the stemness and redox capacity of hMSCs and provides new insight for designing highly scalable, programmable culture platforms for clinical translation.

Humanized Mouse Model of Ebola Virus Disease Mimics the Immune Responses in Human Disease.

PubMed

Bird, Brian H; Spengler, Jessica R; Chakrabarti, Ayan K; Khristova, Marina L; Sealy, Tara K; Coleman-McCray, JoAnn D; Martin, Brock E; Dodd, Kimberly A; Goldsmith, Cynthia S; Sanders, Jeanine; Zaki, Sherif R; Nichol, Stuart T; Spiropoulou, Christina F

2016-03-01

Animal models recapitulating human Ebola virus disease (EVD) are critical for insights into virus pathogenesis. Ebola virus (EBOV) isolates derived directly from human specimens do not, without adaptation, cause disease in immunocompetent adult rodents. Here, we describe EVD in mice engrafted with human immune cells (hu-BLT). hu-BLT mice developed EVD following wild-type EBOV infection. Infection with high-dose EBOV resulted in rapid, lethal EVD with high viral loads, alterations in key human antiviral immune cytokines and chemokines, and severe histopathologic findings similar to those shown in the limited human postmortem data available. A dose- and donor-dependent clinical course was observed in hu-BLT mice infected with lower doses of either Mayinga (1976) or Makona (2014) isolates derived from human EBOV cases. Engraftment of the human cellular immune system appeared to be essential for the observed virulence, as nonengrafted mice did not support productive EBOV replication or develop lethal disease. hu-BLT mice offer a unique model for investigating the human immune response in EVD and an alternative animal model for EVD pathogenesis studies and therapeutic screening. Published by Oxford University Press for the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

A cross-sectional study of the relationships between illness insight, internalized stigma, and suicide risk in individuals with schizophrenia.

PubMed

Sharaf, Amira Y; Ossman, Laila H; Lachine, Ola A

2012-12-01

Suicide is the major cause of premature death among individuals with schizophrenia. Ironically, one factor that heightens suicide risk is insight into mental illness. Little is known, however, about how insight contributes to suicidality. Recent evidence suggests that negative outcomes related to insight might depend on whether or not the individual accepts the stigmatizing beliefs about the mental illness. The present study examined the interactive effects of insight and internalized stigma on suicide risk in individuals with schizophrenia. We hypothesized that insight into mental illness and internalized stigma would increase suicide risk and that internalized stigma would moderate the effect of insight on suicide risk. A cross-sectional design was used in this study. A convenience sample of 200 individuals with schizophrenia was recruited from an outpatient clinic in the Eastern catchment area in Alexandria, Egypt. Eligible study participants were individuals with an illness duration not exceeding ten years, currently in outpatient treatment and follow-up, and post-acute or in a stable phase of their disorder. Individuals provided signed consent to participate and were interviewed to assess suicide risk, insight, internalized stigma of mental illness and depression. Slightly more than 38% of the study participants were classified as having a severe suicide risk. As predicted, suicide risk was positively associated with insight (r=.55, p<.001), internalized stigma (r=.79, p<.001), and depression (r=.78, p<.001). However, the influence of insight was not significant after controlling for covariates in the regression model (β=-.02, ns). Internalized stigma and depression independently predicted suicide risk, explaining 74% of variance in suicide risk, F(change) (6, 191)=11.54, p<.001. Greater insight was significantly linked to increased levels of internalized stigma (r=.59, p<.001) and depression (r=.61, p<.001). Internalized stigma did not moderate the influence of insight on suicide risk. The present study draws attention to the robust influence of internalized stigma in increasing suicide risk and suggests clinical approaches for managing internalized stigma and suicide risk among individuals with schizophrenia. Copyright © 2012 Elsevier Ltd. All rights reserved.

Linking FRRF Derived Photophysiology with Carbon-based Primary Productivity: Insights from Concepts of Cellular Energy Allocation

NASA Astrophysics Data System (ADS)

Schuback, N.; Schallenberg, C.; Duckham, C.; Flecken, M.; Maldonado, M. T.; Tortell, P. D.

2016-02-01

Active chlorophyll a fluorescence approaches, including fast repetition rate fluorometry (FRRF), have the potential to provide estimates of phytoplankton primary productivity at unprecedented spatial and temporal resolution. FRRF-derived productivity rates are based on estimates of charge separation in photosystem II (ETRRCII), which must be converted into ecologically relevant units of carbon fixation. Understanding sources of variability in the coupling of ETRRCII and carbon fixation provides important physiological insight into phytoplankton photosynthesis, and is critical for the application of FRRF as a primary productivity measurement tool. We present data from a series of experiments during which we simultaneously measured phytoplankton carbon fixation and ETRRCII in the iron-limited NE subarctic Pacific. Our results show significant variability of the derived conversion factor (Ve:C/nPSII), with highest values observed under conditions of excess excitation pressure at the level of photosystem II, caused by high light and/or low iron. Our results will be discussed in the context of metabolic plasticity, which evolved in phytoplankton to simultaneously maximize growth and provide photoprotection under fluctuating light and limiting nutrient availabilities. Because the derived conversion factor is associated with conditions of excess light, it correlates with the expression of non-photochemical quenching (NPQ) in the pigment antenna, also derived from FRRF measurements. Our results demonstrate a significant correlation between NPQ and the conversion factor Ve:C/nPSII, and the potential of this relationship to improve FRRF-based estimates of phytoplankton carbon fixation rates is discussed.

Bringing explicit insight into cognitive psychology features during clinical reasoning seminars: a prospective, controlled study.

PubMed

Nendaz, Mathieu R; Gut, Anne M; Louis-Simonet, Martine; Perrier, Arnaud; Vu, Nu V

2011-04-01

Facets of reasoning competence influenced by an explicit insight into cognitive psychology features during clinical reasoning seminars have not been specifically explored. This prospective, controlled study, conducted at the University of Geneva Faculty of Medicine, Switzerland, assessed the impact on sixth-year medical students' patient work-up of case-based reasoning seminars, bringing them explicit insight into cognitive aspects of their reasoning. Volunteer students registered for our three-month Internal Medicine elective were assigned to one of two training conditions: standard (control) or modified (intervention) case-based reasoning seminars. These seminars start with the patient's presenting complaint and the students must ask the tutor for additional clinical information to progress through case resolution. For this intervention, the tutors made each step explicit to students and encouraged self-reflection on their reasoning processes. At the end of their elective, students' performances were assessed through encounters with two standardized patients and chart write-ups. Twenty-nine students participated, providing a total of 58 encounters. The overall differences in accuracy of the final diagnosis given to the patient at the end of the encounter (control 63% vs intervention 74%, p = 0.53) and of the final diagnosis mentioned in the patient chart (61% vs 70%, p = 0.58) were not statistically significant. The students in the intervention group significantly more often listed the correct diagnosis among the differential diagnoses in their charts (75% vs 97%, p = 0.02). This case-based clinical reasoning seminar intervention, designed to bring students insight into cognitive features of their reasoning, improved aspects of diagnostic competence.

Key principles for a national clinical decision support knowledge sharing framework: synthesis of insights from leading subject matter experts

PubMed Central

Hongsermeier, Tonya; Wright, Adam; Lewis, Janet; Bell, Douglas S; Middleton, Blackford

2013-01-01

Objective To identify key principles for establishing a national clinical decision support (CDS) knowledge sharing framework. Materials and methods As part of an initiative by the US Office of the National Coordinator for Health IT (ONC) to establish a framework for national CDS knowledge sharing, key stakeholders were identified. Stakeholders' viewpoints were obtained through surveys and in-depth interviews, and findings and relevant insights were summarized. Based on these insights, key principles were formulated for establishing a national CDS knowledge sharing framework. Results Nineteen key stakeholders were recruited, including six executives from electronic health record system vendors, seven executives from knowledge content producers, three executives from healthcare provider organizations, and three additional experts in clinical informatics. Based on these stakeholders' insights, five key principles were identified for effectively sharing CDS knowledge nationally. These principles are (1) prioritize and support the creation and maintenance of a national CDS knowledge sharing framework; (2) facilitate the development of high-value content and tooling, preferably in an open-source manner; (3) accelerate the development or licensing of required, pragmatic standards; (4) acknowledge and address medicolegal liability concerns; and (5) establish a self-sustaining business model. Discussion Based on the principles identified, a roadmap for national CDS knowledge sharing was developed through the ONC's Advancing CDS initiative. Conclusion The study findings may serve as a useful guide for ongoing activities by the ONC and others to establish a national framework for sharing CDS knowledge and improving clinical care. PMID:22865671

Design of novel HIV-1 protease inhibitors incorporating isophthalamide-derived P2-P3 ligands: Synthesis, biological evaluation and X-ray structural studies of inhibitor-HIV-1 protease complex

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ghosh, Arun K.; Brindisi, Margherita; Nyalapatla, Prasanth R.

Based upon molecular insights from the X-ray structures of inhibitor-bound HIV-1 protease complexes, we have designed a series of isophthalamide-derived inhibitors incorporating substituted pyrrolidines, piperidines and thiazolidines as P2-P3 ligands for specific interactions in the S2-S3 extended site. Compound 4b has shown an enzyme Ki of 0.025 nM and antiviral IC50 of 69 nM. An X-ray crystal structure of inhibitor 4b-HIV-1 protease complex was determined at 1.33 Å resolution. We have also determined X-ray structure of 3b-bound HIV-1 protease at 1.27 Å resolution. These structures revealed important molecular insight into the inhibitor–HIV-1 protease interactions in the active site.

The Beck Cognitive Insight Scale (BCIS): translation and validation of the Taiwanese version.

PubMed

Kao, Yu-Chen; Liu, Yia-Ping

2010-04-09

Over the last few decades, research concerning the insight of patients with schizophrenia and its relationships with other clinical variables has been given much attention in the clinical setting. Since that time, a series of instruments assessing insight have been developed. The purpose of this study was to examine the reliability and validity of the Taiwanese version of the Beck Cognitive Insight Scale (BCIS). The BCIS is a self-administered instrument designed to evaluate cognitive processes that involves reevaluating patients' anomalous experiences and specific misinterpretations. The English language version of the BCIS was translated into Taiwanese for use in this study. A total of 180 subjects with and without psychosis completed the Taiwanese version of the BCIS and additional evaluations to assess researcher-rated insight scales and psychopathology. Psychometric properties (factor structures and various types of reliability and validity) were assessed for this translated questionnaire. Overall, the Taiwanese version of the BCIS showed good reliability and stability over time. This translated scale comprised a two-factor solution corresponding to reflective attitude and certain attitude subscales. Following the validation of the internal structure of the scale, we obtained an R-C (reflective attitude minus certain attitude) index of the translated BCIS, representing the measurement of cognitive insight by subtracting the score of the certain attitude subscale from that of the reflective attitude subscale. As predicted, the differences in mean reflective attitude, certain attitude and R-C index between subjects with and without psychosis were significant. Our data also demonstrated that psychotic patients were significantly less reflective, more confident in their beliefs, and had less cognitive insight compared with nonpsychotic control groups. In light of these findings, we believe that the Taiwanese version of BCIS is a valid and reliable instrument for the assessment of cognitive insight in psychotic patients.

Assessment of Genetics Knowledge and Skills in Medical Students: Insight for a Clinical Neurogenetics Curriculum

ERIC Educational Resources Information Center

Pearl, Phillip L.; Pettiford, Jennifer M.; Combs, Susan E.; Heffron, Ari; Healton, Sean; Hovaguimian, Alexandra; Macri, Charles J.

2011-01-01

The pace of discovery in biochemistry and genetics and its effect on clinical medicine places new curricular challenges in medical school education. We sought to evaluate students' understanding of neurogenetics and its clinical applications to design a pilot curriculum into the clinical neurology clerkship. We utilized a needs assessment and a…

Mind, brain and body. Healing trauma: the way forward.

PubMed

Wilkinson, Margaret

2017-09-01

The paper explores an interdisciplinary whole person approach to healing from trauma that conserves our rich inheritance from Jung but also takes on board insights from research in the areas of attachment, trauma and the neurobiology of emotion. It is now over 20 years since insights from neurobiology began to be used to inform clinical practice. The paper reviews key insights which have emerged, along with the ways they enable therapists to help mind, brain and body to heal and the ways in which they clarify why, in clinical practice, we do what we do. Traditionally the emphasis has been on words, interpretations, and meaning-making. Currently there is greater appreciation of the affective, relational, embodied aspects of therapeutic work and the way in which these relate to traumatic early interactive experience that is held outside of human awareness. The ways in which knowledge of particular systems of connectivity inform understanding of the whole mind-brain-body relationship are examined. The way forward for clinical practice to become more focused in order to help clients to heal in mind and body is reviewed. © 2017, The Society of Analytical Psychology.

Microbiota of Cow’s Milk; Distinguishing Healthy, Sub-Clinically and Clinically Diseased Quarters

PubMed Central

Oikonomou, Georgios; Bicalho, Marcela Lucas; Meira, Enoch; Rossi, Rodolfo Elke; Foditsch, Carla; Machado, Vinicius Silva; Teixeira, Andre Gustavo Vieira; Santisteban, Carlos; Schukken, Ynte Hein; Bicalho, Rodrigo Carvalho

2014-01-01

The objective of this study was to use pyrosequencing of the 16S rRNA genes to describe the microbial diversity of bovine milk samples derived from clinically unaffected quarters across a range of somatic cell counts (SCC) values or from clinical mastitis, culture negative quarters. The obtained microbiota profiles were used to distinguish healthy, subclinically and clinically affected quarters. Two dairy farms were used for the collection of milk samples. A total of 177 samples were used. Fifty samples derived from healthy, culture negative quarters with a SCC of less than 20,000 cells/ml (group 1); 34 samples derived from healthy, culture negative quarters, with a SCC ranging from 21,000 to 50,000 cells/ml (group 2); 26 samples derived from healthy, culture negative quarters with a SCC greater than 50,000 cells/ml (group 3); 34 samples derived from healthy, culture positive quarters, with a SCC greater than 400,000 (group 4, subclinical); and 33 samples derived from clinical mastitis, culture negative quarters (group 5, clinical). Bacterial DNA was isolated from these samples and the 16S rRNA genes were individually amplified and pyrosequenced. All samples analyzed revealed great microbial diversity. Four bacterial genera were present in every sample obtained from healthy quarters (Faecalibacterium spp., unclassified Lachnospiraceae, Propionibacterium spp. and Aeribacillus spp.). Discriminant analysis models showed that samples derived from healthy quarters were easily discriminated based on their microbiota profiles from samples derived from clinical mastitis, culture negative quarters; that was also the case for samples obtained from different farms. Staphylococcus spp. and Streptococcus spp. were among the most prevalent genera in all groups while a general multivariable linear model revealed that Sphingobacterium and Streptococcus prevalences were associated with increased 10 log SCC. Conversely, Nocardiodes and Paenibacillus were negatively correlated, and a higher percentage of the genera was associated with a lower 10 log SCC. PMID:24465777

Listening with a narrative ear: Insights from a study of fall stories in older adults.

PubMed

Pereles, Laurie; Jackson, Roberta; Rosenal, Tom; Nixon, Lara

2017-01-01

To determine the value of adding a patient narrative to the clinical assessment of falls in the elderly. Qualitative study of interviews. A fall prevention clinic in Calgary, Alta. Fifteen older adults on a wait list for assessment by the fall clinic and the physiotherapists who assessed them. Participants' stories were audiorecorded and later transcribed and summarized. Stories were collected using open-ended questions, first inviting participants to tell the interviewer about themselves, and then the circumstances of their falls and their reflections on them. In a subsequent visit, transcriptions or summaries were returned to patients for member checking. Narratives were read and analyzed by all 4 investigators using a narrative approach and a close-reading technique. With the patients' additional consent, stories were shared with the fall prevention team for their insights and reactions. Interviews with physiotherapists were audiorecorded and transcribed. The narrative analysis provided new insights into the attitudes about and perceptions of the causes of falls, their effects, and rehabilitation. Close reading exposed presentation of self, locus of control, and underlying social and emotional issues. The addition of patient narratives to clinical assessments offers clinicians an understanding of patients' perspectives, which can be used to better engage patients in rehabilitation. Copyright© the College of Family Physicians of Canada.

Lack of irrefutable validation does not negate clinical utility of near-infrared spectroscopy monitoring: learning to trust new technology.

PubMed

Kane, Jason M; Steinhorn, David M

2009-09-01

Reliance on new monitoring device technology is based upon an understanding of how the device operates and its reliability in a specific clinical setting. The introduction of new monitoring devices will therefore elicit either distrust of the new technology and the data presented or adoption of new devices. The use of near-infrared spectroscopy (NIRS) technology to monitor vital organs in postoperative pediatric cardiac surgery patients has been extensively described yet controversy remains as to the use of this monitoring device. The following retrospective case series demonstrates how learning from trends in data elicited from 2-site NIRS monitoring provided important bedside insights. These insights led to changes in clinician behavior and reliance on NIRS monitoring for early recognition of clinically silent deteriorations. Disregard for the NIRS data may have led to a fatal outcome in an unstable patient who might have received more timely intervention if the NIRS data had been acknowledged earlier. This case series demonstrates that 2-site NIRS monitoring accurately reflects situations in which poor clinical outcomes may occur when declining trends in somatic tissue oxygen saturations are not corrected. Physician management of the postoperative pediatric cardiac surgery patient can change based upon the insights gained through the application of NIRS monitoring.

Measuring Sustainability: Deriving Metrics From Objectives (Presentation)

EPA Science Inventory

The definition of 'sustain', to keep in existence, provides some insight into the metrics that are required to measure sustainability and adequately respond to assure sustainability. Keeping something in existence implies temporal and spatial contexts and requires metrics that g...

Effector T-cell infiltration positively impacts survival of glioblastoma patients and is impaired by tumor-derived TGF-β.

PubMed

Lohr, Jennifer; Ratliff, Thomas; Huppertz, Andrea; Ge, Yingzi; Dictus, Christine; Ahmadi, Rezvan; Grau, Stefan; Hiraoka, Nobuyoshi; Eckstein, Volker; Ecker, Rupert C; Korff, Thomas; von Deimling, Andreas; Unterberg, Andreas; Beckhove, Philipp; Herold-Mende, Christel

2011-07-01

In glioma-in contrast to various other cancers-the impact of T-lymphocytes on clinical outcome is not clear. We investigated the clinical relevance and regulation of T-cell infiltration in glioma. T-cell subpopulations from entire sections of 93 WHO°II-IV gliomas were computationally identified using markers CD3, CD8, and Foxp3; survival analysis was then done on primary glioblastomas (pGBM). Endothelial cells expressing cellular adhesion molecules (CAM) were similarly computationally quantified from the same glioma tissues. Influence of prominent cytokines (as measured by ELISA from 53 WHO°II-IV glioma lysates) on CAM-expression in GBM-isolated endothelial cells was determined using flow cytometry. The functional relevance of the cytokine-mediated CAM regulation was tested in a transmigration assay using GBM-derived endothelial cells and autologous T-cells. Infiltration of all T-cell subsets increased in high-grade tumors. Most strikingly, within pGBM, elevated numbers of intratumoral effector T cells (T(eff), cytotoxic and helper) significantly correlated with a better survival; regulatory T cells were infrequently present and not associated with GBM patient outcome. Interestingly, increased infiltration of T(eff) cells was related to the expression of ICAM-1 on the vessel surface. Transmigration of autologous T cells in vitro was markedly reduced in the presence of CAM-blocking antibodies. We found that TGF-β molecules impeded transmigration and downregulated CAM-expression on GBM-isolated endothelial cells; blocking TGF-β receptor signaling increased transmigration. This study provides comprehensive and novel insights into occurrence and regulation of T-cell infiltration in glioma. Specifically, targeting TGF-β1 and TGF-β2 might improve intratumoral T-cell infiltration and thus enhance effectiveness of immunotherapeutic approaches.

Synergistic Antiproliferative Effects of a New Cucurbitacin B Derivative and Chemotherapy Drugs on Lung Cancer Cell Line A549.

PubMed

Marostica, Lucas Lourenço; Silva, Izabella Thaís; Kratz, Jadel Müller; Persich, Lara; Geller, Fabiana Cristina; Lang, Karen Luise; Caro, Miguel Soriano Balparda; Durán, Fernando Javier; Schenkel, Eloir Paulo; Simões, Cláudia Maria Oliveira

2015-10-19

Nonsmall cell lung cancer (NSCLC) represents an important cause of mortality worldwide due to its aggressiveness and growing resistance to currently available therapy. Cucurbitacins have emerged as novel potential anticancer agents showing strong antiproliferative effects and can be promising candidates for combined treatments with clinically used anticancer agents. This study investigates the synergistic antiproliferative effects of a new semisynthetic derivative of cucurbitacin B (DACE) with three chemotherapy drugs: cisplatin (CIS), irinotecan (IRI), and paclitaxel (PAC) on A549 cells. The most effective combinations were selected for studies of the mechanism of action. Using an in silico tool, DACE seems to act by a different mechanism of action when compared with that of different classes of drugs already used in clinical settings. DACE also showed potent synergic effects with drugs, and the most potent combinations induced G2/M cell cycle arrest by modulating survivin and p53 expression, disruption of F-actin cytoskeleton, and cell death by apoptosis. These treatments completely inhibited the clonogenic potential and did not reduce the proliferation of nontumoral lung cells (MRC-5). DACE also showed relevant antimigratory and anti-invasive effects, and combined treatments modulated cell migration signaling pathways evolved with metastasis progression. The effects of DACE associated with drugs was potentiated by the oxidant agent l-buthionine-sulfoximine (BSO), and attenuated by N-acetilcysteine (NAC), an antioxidant agent. The antiproliferative effects induced by combined treatments were attenuated by a pan-caspase inhibitor, indicating that the effects of these treatments are dependent on caspase activity. Our data highlight the therapeutic potential of DACE used in combination with known chemotherapy drugs and offer important insights for the development of more effective and selective therapies against lung cancer.

Murabutide revisited: a review of its pleiotropic biological effects.

PubMed

Jakopin, Žiga

2013-01-01

Despite the great efforts put into their development, the list of clinically approved immunological adjuvants is still very short. Evolution of the knowledge of the immune system has enabled for rational design of novel adjuvants and has led to the conclusion that more than one type of adjuvant will be required. Derivatives of muramyl dipeptide (MDP), the minimal immunomodulatory structure of bacterial cell wall peptidoglycan, have gained considerable attention in the past decades, because of their potent adjuvant effects. Murabutide is a safe derivative of MDP, which interacts with cells of the immune system, both innate and adaptive, and exerts its effect through activation of Nod2. The transcriptional response of murabutide-stimulated macrophages revealed enhanced expression of genes coding for various proteins such as immune mediators and their receptors, transcription factors and kinases, ion channels/transporters and proteins involved in cell metabolic activity, thus reflecting a broad spectrum of biological effects. In addition to its well recognized adjuvant effect, murabutide has also been shown to enhance the host's resistance against microbial infections, nonspecific resistance against tumors and the induction of cytokines and chemokines implicated in enhancing the immune response and hematopoesis. This article provides an insight into the mechanism of action of murabutide and its interactions with the cells of the immune system in vitro and in vivo. On account of its numerous biological effects, murabutide has been the subject of several clinical studies. Many of these have confirmed its potential to synergize with cytokines of therapeutic interest in potentiating the tumoricidal activity of macrophages or targeting chronic viral diseases, as well as reducing the cytokine dosage needed to achieve a therapeutic effect. This review covers the findings of all relevant studies and focuses on the role of murabutide and its potential in the treatment of several microbial diseases.

[Autistic dimension in obsessive-compulsive disorder in adolescence].

PubMed

Ardizzone, Ignazio; Soletti, Laura; Panunzi, Sara; Carratelli, Teresa I

2010-01-01

This study examines the obsessive-compulsive disorder (OCD) with normal and poor insight of illness and it detects the presence of autistic traits. The aim is to establish the relationship between OCD and Autistic Spectrum Disorder (ASD): comorbidity or subtype of OCD? The sample consists of 48 adolescents (aged 12-18) with a clinical diagnosis of OCD (according DSM-IV-TR). After administering the Children's Yale Brown Obsessive-Compulsive Scale (CYBOCS) and the Brown Assessement Beliefs Scale (BABS), the sample is divided into two groups according to insight of illness. Autism Diagnostic Observation Schedule (ADOS) and Social Communication Questionnaire (SCQ) were used to assist in the ASD diagnosis; Structured Clinical Interview for DSM-IV Axis II Personality Disorders (SCID-II) was administered to assess personality disorders. 47% of subjects presents poor insight and 27% are included within the diagnostic criteria for autistic spectrum disorder. Poor insight in obsessive-compulsive symptoms is significantly associated with the presence of autistic traits. There is also a significant association between cluster hoarding and poor insight. This study suggests the existence of an obsessive autistic atypical subtype, where the compulsive dimension of repetitive behaviours vanishes in an autistic dimension with stereotyped manifestations. Further research should be conducted to better understand this obsessive autistic atypical subtype and to put it in the obsessive-compulsive spectrum in adolescence.

Traumatic injuries of prehistoric teeth: new evidence from Baluchistan and Punjab Provinces, Pakistan.

PubMed

Lukacs, J R; Hemphill, B E

1990-01-01

Traumatic lesions of the dentition are rarely reported, while skeletal trauma constitutes a significant portion of the paleopathology literature. The purpose of this paper is to show how meticulous analysis of traumatic dental lesions can provide insights into patterns of behavior in prehistory. Two cases of dental trauma from prehistoric Pakistan illustrate some crucial problems in diagnosing the etiology of traumatic lesions. Bio-behavioral insights derived from the analysis of dental trauma compliment inferences gleaned from more traditional approaches, including the study of dental attrition and dental morphology.

Concise Review: Cardiac Disease Modeling Using Induced Pluripotent Stem Cells.

PubMed

Yang, Chunbo; Al-Aama, Jumana; Stojkovic, Miodrag; Keavney, Bernard; Trafford, Andrew; Lako, Majlinda; Armstrong, Lyle

2015-09-01

Genetic cardiac diseases are major causes of morbidity and mortality. Although animal models have been created to provide some useful insights into the pathogenesis of genetic cardiac diseases, the significant species differences and the lack of genetic information for complex genetic diseases markedly attenuate the application values of such data. Generation of induced pluripotent stem cells (iPSCs) from patient-specific specimens and subsequent derivation of cardiomyocytes offer novel avenues to study the mechanisms underlying cardiac diseases, to identify new causative genes, and to provide insights into the disease aetiology. In recent years, the list of human iPSC-based models for genetic cardiac diseases has been expanding rapidly, although there are still remaining concerns on the level of functionality of iPSC-derived cardiomyocytes and their ability to be used for modeling complex cardiac diseases in adults. This review focuses on the development of cardiomyocyte induction from pluripotent stem cells, the recent progress in heart disease modeling using iPSC-derived cardiomyocytes, and the challenges associated with understanding complex genetic diseases. To address these issues, we examine the similarity between iPSC-derived cardiomyocytes and their ex vivo counterparts and how this relates to the method used to differentiate the pluripotent stem cells into a cardiomyocyte phenotype. We progress to examine categories of congenital cardiac abnormalities that are suitable for iPSC-based disease modeling. © AlphaMed Press.

Exploring molecular insights into the interaction mechanism of cholesterol derivatives with the Mce4A: A combined spectroscopic and molecular dynamic simulation studies.

PubMed

Khan, Shagufta; Khan, Faez Iqbal; Mohammad, Taj; Khan, Parvez; Hasan, Gulam Mustafa; Lobb, Kevin A; Islam, Asimul; Ahmad, Faizan; Imtaiyaz Hassan, Md

2018-05-01

Mammalian cell entry protein (Mce4A) is a member of MCE-family, and is being considered as a potential drug target of Mycobacterium tuberculosis infection because it is required for invasion and latent survival of pathogen by utilizing host's cholesterol. In the present study, we performed molecular docking followed by 100 ns MD simulation studies to understand the mechanism of interaction of Mce4A to the cholesterol derivatives and probucol. The selected ligands, cholesterol, 25-hydroxycholesterol, 5-cholesten-3β-ol-7-one and probucol bind to the predicted active site cavity of Mce4A, and complexes remain stable during entire simulation of 100 ns. In silico studies were further validated by fluorescence-binding studies to calculate actual binding affinity and number of binding site(s). The non-toxicity of all ligands was confirmed on human monocytic cell (THP1) by MTT assay. This work provides a deeper insight into the mechanism of interaction of Mce4A to cholesterol derivatives, which may be further exploited to design potential and specific inhibitors to ameliorate the Mycobacterium pathogenesis. Copyright © 2018 Elsevier B.V. All rights reserved.

Metronidazole within phosphatidylcholine lipid membranes: new insights to improve the design of imidazole derivatives.

PubMed

Lopes-de-Campos, Daniela; Nunes, Cláudia; Sarmento, Bruno; Jakobtorweihen, Sven; Reis, Salette

2018-05-30

Metronidazole is a benzimidazole derivative with antibacterial and antiprotozoal activity. Despite its therapeutic efficacy, several studies have been developing new imidazole derivatives with lower toxicity. Considering that drug-membrane interactions are key factors for drugs pharmacokinetic and pharmacodynamic properties, the aim of this work is to provide new insights into the structure-toxicity relationships of metronidazole within phosphatidylcholine membranes. For that purpose, lipid membrane models (liposomes and monolayers) composed of dipalmitoylphosphatidylcholine were used. Experimental techniques (determination of partition coefficients and Langmuir isotherm measurements) were combined with molecular dynamics simulations. Different pHs and lipid phases were evaluated to enable a better extrapolation for in vivo conditions. The partition of metronidazole depends on the pH and on the biphasic system (octanol/water or DPPC/water system). At pH 1.2, metronidazole is hydrophilic. At pH 7.4, metronidazole disturbs the order and the packing of phospholipids. For this toxic effect, the hydroxyl group of the side chain of metronidazole is a key by interacting with the water embedded in the membrane and with the phosphate group and the apolar chains of phospholipids. Copyright © 2018. Published by Elsevier B.V.

Visual communication in the psychoanalytic situation.

PubMed

Kanzer, M

1980-01-01

The relationship between verbal and visual aspects of the analytic proceedings shows them blended integrally in the experiences of both patient and analyst and in contributing to the insights derived during the treatment. Areas in which the admixture of the verbal and visual occur are delineated. Awareness of the visual aspects gives substance to the operations of empathy, intuition, acting out, working through, etc. Some typical features of visual 'language" are noted and related to the analytic situation. As such they can be translated with the use of logic and consciousness on the analyst's part, not mere random eruptions of intuition. The original significance of dreams as a royal road to the unconscious is confirmed-but we also find in them insights to be derived with higher mental processes. Finally, dyadic aspects of the formation and aims of dreams during analysis are pointed out, with important implications for the analyst's own self-supervision of his techniques and 'real personality" and their effects upon the patient. how remarkable that Dora's dreams, all too belatedly teaching Freud about their transference implications, still have so much more to communicate that derives from his capacity to record faithfully observations he was not yet ready to explain.

International survey among orthopaedic trauma surgeons: Lack of a definition of fracture-related infection.

PubMed

Morgenstern, M; Moriarty, T F; Kuehl, R; Richards, R G; McNally, M A; Verhofstad, M H J; Borens, O; Zalavras, C; Raschke, M; Kates, S L; Metsemakers, W J

2018-03-01

Fracture-related infection (FRI) is one of the most challenging musculoskeletal complications in orthopaedic-trauma surgery. Although the orthopaedic community has developed and adopted a consensus definition of prosthetic joint infections (PJI), it still remains unclear how the trauma surgery community defines FRI in daily clinical practice or in performing clinical research studies. The central aim of this study was to survey the opinions of a global network of trauma surgeons on the definitions and criteria they routinely use, and their opinion on the need for a unified definition of FRI. The secondary aims were to survey their opinion on the utility of currently used definitions that may be at least partially applicable for FRI, and finally their opinion on the important clinical parameters that should be considered as diagnostic criteria for FRI. An 11-item questionnaire was developed to cover the above-mentioned aims. The questionnaire was administered by SurveyMonkey and was sent via blast email to all registered users of AO Trauma (Davos, Switzerland). Out of the 26'563 recipients who opened the email, 2'327 (8.8%) completed the questionnaire. Nearly 90% of respondents agreed that a consensus-derived definition for FRI is required and 66% of the surgeons also agreed that PJI and FRI are not equal with respect to diagnosis, treatment and outcome. Furthermore, "positive cultures from microbiology testing", "elevation of CRP", "purulent drainage" and "local clinical signs of infection" were voted the most important diagnostic parameters for FRI. This international survey infers the need for a consensus definition of FRI and provides insight into the clinical parameters seen by an international community of trauma surgeons as being critical for defining FRI. Copyright © 2018 Elsevier Ltd. All rights reserved.

Marine-derived angiogenesis inhibitors for cancer therapy.

PubMed

Wang, Ying-Qing; Miao, Ze-Hong

2013-03-15

Angiogenesis inhibitors have been successfully used for cancer therapy in the clinic. Many marine-derived natural products and their analogues have been reported to show antiangiogenic activities. Compared with the drugs in the clinic, these agents display interesting characteristics, including diverse sources, unique chemical structures, special modes of action, and distinct activity and toxicity profiles. This review will first provide an overview of the current marine-derived angiogenesis inhibitors based on their primary targets and/or mechanisms of action. Then, the marine-derived antiangiogenic protein kinase inhibitors will be focused on. And finally, the clinical trials of the marine-derived antiangiogenic agents will be discussed, with special emphasis on their application potentials, problems and possible coping strategies in their future development as anticancer drugs.

Bolide Airbursts as a Seismic Source for the 2018 Mars InSight Mission

NASA Astrophysics Data System (ADS)

Stevanović, J.; Teanby, N. A.; Wookey, J.; Selby, N.; Daubar, I. J.; Vaubaillon, J.; Garcia, R.

2017-10-01

In 2018, NASA will launch InSight, a single-station suite of geophysical instruments, designed to characterise the martian interior. We investigate the seismo-acoustic signal generated by a bolide entering the martian atmosphere and exploding in a terminal airburst, and assess this phenomenon as a potential observable for the SEIS seismic payload. Terrestrial analogue data from four recent events are used to identify diagnostic airburst characteristics in both the time and frequency domain. In order to estimate a potential number of detectable events for InSight, we first model the impactor source population from observations made on the Earth, scaled for planetary radius, entry velocity and source density. We go on to calculate a range of potential airbursts from the larger incident impactor population. We estimate there to be {˜} 1000 events of this nature per year on Mars. To then derive a detectable number of airbursts for InSight, we scale this number according to atmospheric attenuation, air-to-ground coupling inefficiencies and by instrument capability for SEIS. We predict between 10-200 detectable events per year for InSight.

The Impact of Clinical Experiences from Athletic Training Student and Preceptor Perspectives

ERIC Educational Resources Information Center

Benes, Sarah S.; Mazerolle, Stephanie M.; Bowman, Thomas G.

2014-01-01

Context: Clinical education is an integral part of athletic training programs. This is where students should develop their professional identities and become socialized into the profession. Understanding the student and preceptor perspectives of the impact that clinical experiences have on students can provide valuable insight into this aspect of…

High-throughput screening of tyrosine kinase inhibitor cardiotoxicity with human induced pluripotent stem cells.

PubMed

Sharma, Arun; Burridge, Paul W; McKeithan, Wesley L; Serrano, Ricardo; Shukla, Praveen; Sayed, Nazish; Churko, Jared M; Kitani, Tomoya; Wu, Haodi; Holmström, Alexandra; Matsa, Elena; Zhang, Yuan; Kumar, Anusha; Fan, Alice C; Del Álamo, Juan C; Wu, Sean M; Moslehi, Javid J; Mercola, Mark; Wu, Joseph C

2017-02-15

Tyrosine kinase inhibitors (TKIs), despite their efficacy as anticancer therapeutics, are associated with cardiovascular side effects ranging from induced arrhythmias to heart failure. We used human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), generated from 11 healthy individuals and 2 patients receiving cancer treatment, to screen U.S. Food and Drug Administration-approved TKIs for cardiotoxicities by measuring alterations in cardiomyocyte viability, contractility, electrophysiology, calcium handling, and signaling. With these data, we generated a "cardiac safety index" to reflect the cardiotoxicities of existing TKIs. TKIs with low cardiac safety indices exhibit cardiotoxicity in patients. We also derived endothelial cells (hiPSC-ECs) and cardiac fibroblasts (hiPSC-CFs) to examine cell type-specific cardiotoxicities. Using high-throughput screening, we determined that vascular endothelial growth factor receptor 2 (VEGFR2)/platelet-derived growth factor receptor (PDGFR)-inhibiting TKIs caused cardiotoxicity in hiPSC-CMs, hiPSC-ECs, and hiPSC-CFs. With phosphoprotein analysis, we determined that VEGFR2/PDGFR-inhibiting TKIs led to a compensatory increase in cardioprotective insulin and insulin-like growth factor (IGF) signaling in hiPSC-CMs. Up-regulating cardioprotective signaling with exogenous insulin or IGF1 improved hiPSC-CM viability during cotreatment with cardiotoxic VEGFR2/PDGFR-inhibiting TKIs. Thus, hiPSC-CMs can be used to screen for cardiovascular toxicities associated with anticancer TKIs, and the results correlate with clinical phenotypes. This approach provides unexpected insights, as illustrated by our finding that toxicity can be alleviated via cardioprotective insulin/IGF signaling. Copyright © 2017, American Association for the Advancement of Science.

Equilibrium Distribution Functions: Another Look.

ERIC Educational Resources Information Center

Waite, Boyd A.

1986-01-01

Discusses equilibrium distribution functions and provides an alternative "derivation" that allows the student, with the help of a computer, to gain intuitive insight as to the nature of distributions in general and the precise nature of the dominance of the Boltzmann distribution. (JN)

More insight into critical wetting in polymer blends

NASA Astrophysics Data System (ADS)

Jerry, Rocco A.; Nauman, E. Bruce

1992-11-01

We have shown that a free energy expression that contains a derivative-dependent boundary penalty term, as introduced by Cohen and Muthukumar [J. Chem. Phys. 90, 5749 (1989)], will extend the region of parameter space over which critical wetting should occur.

Advanced clinical insights & practice: ischemic heart disease.

PubMed

Benner, Randall W; Zavarella, Matthew S

2008-03-01

This issue sees the debut of a new series of continuing education articles. The series, Advanced Clinical Insights & Practice, is designed to provide continuing education to an ever-expanding realm of paramedicine that needs more of it: the critical care transport paramedic. Secondly, and equally important, are the benefits that can be reaped by other certification levels reading this feature. For EMT-Basics and Intermediates, it will provide a great enhancement to your core knowledge, although most of the interventions discussed will be beyond your traditional scope. For paramedics, it will augment both your pathophysiological understanding and clinical assessment/management skills of diseases and injuries discussed. Ultimately though, it is hoped that anyone who reads these articles will become a better clinician. The next article will appear in the July issue.

Insights into the Functional Anatomy Behind the PREEMPT Injection Paradigm: Guidance on Achieving Optimal Outcomes.

PubMed

Blumenfeld, Andrew M; Silberstein, Stephen D; Dodick, David W; Aurora, Sheena K; Brin, Mitchell F; Binder, William J

2017-05-01

To provide clinically relevant insights on the identification of the muscles and techniques involved in the safe and effective use of onabotulinumtoxinA for chronic migraine prophylaxis. Although guidance on the use of onabotulinumtoxinA for chronic migraine is available, based on the Phase III Research Evaluating Migraine Prophylaxis Therapy (PREEMPT) clinical program, clinical experience has shown that insufficient understanding of the anatomy and function of the head and neck muscles may lead to undesirable outcomes and suboptimal efficacy. Each muscle involved in the standardized PREEMPT injection paradigm is reviewed with a thorough description of each muscle's anatomy (ie, muscle description and location, innervation, vascular supply) and function. Key insights based on clinical experience are also provided to help improve outcomes. The identification of the muscles in the PREEMPT injection paradigm should be based on each patient's unique anatomy and injections should be administered using the advised techniques. A thorough examination of the patient prior to treatment is also critical to determine if any preexisting conditions may increase the risk for unwanted outcomes and appropriate expectations should be communicated. Thorough knowledge of the functional anatomy of the muscles involved in the standardized PREEMPT injection paradigm is critical to achieve the efficacy and safety observed in clinical trials. In addition, it is important to assess a patient's baseline condition to anticipate the risk for unwanted outcomes that may result from treatment. © 2017 Allergan plc. Headache published by Wiley Periodicals, Inc. on behalf of American Headache Society.

Insights into the Functional Anatomy Behind the PREEMPT Injection Paradigm: Guidance on Achieving Optimal Outcomes

PubMed Central

Silberstein, Stephen D.; Dodick, David W.; Aurora, Sheena K.; Brin, Mitchell F.; Binder, William J.

2017-01-01

Objective To provide clinically relevant insights on the identification of the muscles and techniques involved in the safe and effective use of onabotulinumtoxinA for chronic migraine prophylaxis. Background Although guidance on the use of onabotulinumtoxinA for chronic migraine is available, based on the Phase III Research Evaluating Migraine Prophylaxis Therapy (PREEMPT) clinical program, clinical experience has shown that insufficient understanding of the anatomy and function of the head and neck muscles may lead to undesirable outcomes and suboptimal efficacy. Design/Methods Each muscle involved in the standardized PREEMPT injection paradigm is reviewed with a thorough description of each muscle's anatomy (ie, muscle description and location, innervation, vascular supply) and function. Key insights based on clinical experience are also provided to help improve outcomes. Results The identification of the muscles in the PREEMPT injection paradigm should be based on each patient's unique anatomy and injections should be administered using the advised techniques. A thorough examination of the patient prior to treatment is also critical to determine if any preexisting conditions may increase the risk for unwanted outcomes and appropriate expectations should be communicated. Conclusions Thorough knowledge of the functional anatomy of the muscles involved in the standardized PREEMPT injection paradigm is critical to achieve the efficacy and safety observed in clinical trials. In addition, it is important to assess a patient's baseline condition to anticipate the risk for unwanted outcomes that may result from treatment. PMID:28387038

Metabolic syndrome and adverse clinical outcomes in patients with bipolar disorder.

PubMed

Bai, Ya-Mei; Li, Cheng-Ta; Tsai, Shih-Jen; Tu, Pei-Chi; Chen, Mu-Hong; Su, Tung-Ping

2016-12-15

Metabolic syndrome (MetS) is highly prevalent among patients with bipolar disorder. MetS may cause complications in the brain, but studies investigating MetS-associated clinical psychiatric outcomes remain scant. We enrolled clinically stable outpatients with bipolar disorder aged 18-65 years and performed anthropometric and fasting biochemical assessments to investigate MetS prevalence. We then performed clinical assessments by using the Young Mania Rating Scale for manic symptoms, the Montgomery-Åsberg Depression Rating Scale for depressive symptoms, the Positive and Negative Symptom Scale for psychotic symptoms, the Involuntary Movement Scale for tardive dyskinesia, the Barnes Akathisia Rating Scale for akathisia, the Udvalg for Kliniske Undersogelser for general side effects, the Schedule for Assessment of Insight for insight, the Global Assessment of Functioning scale for global functioning, and the Wisconsin Card Sorting Test (WCST) for cognitive executive function. In total, 143 patients were enrolled and had a MetS prevalence of 29.4%. The patients treated with atypical antipsychotics plus mood stabilizers (36.3%) and atypical antipsychotics alone (36.0%) had a significantly higher prevalence of MetS than did those treated with mood stabilizers alone (10.5%; p = 0.012). According to multivariate regression analyses adjusted for age, sex, smoking status, bipolar disorder subtype (I or II), pharmacological treatment duration, and psychiatric medication, compared with patients without MetS, those with MetS had significantly more previous hospitalizations (p = 0.036), severer tardive dyskinesia (p = 0.030), poorer insight (p = 0.036), poorer global function (p = 0.046), and more impaired executive function (conceptual level response on the WCST; p = 0.042). Our results indicated that patients with comorbid bipolar disorder and MetS have more adverse clinical outcomes than those without, with more hospitalizations, severer tardive dyskinesia, poorer insight, poorer global function, and more impaired executive function. Monitoring MetS is crucial for assessing not only physical burden, but also psychiatric outcomes.

[Relationship between insight, violence and diagnoses in psychotic patients].

PubMed

Lera Calatayud, Guillem; Herrero Sebastián, Neus; Aguilar García-Iturrospe, Eduardo; González Piqueras, José Carlos; Sanjuán Arias, Julio; Leal Cercós, Carmen

2012-01-01

Lack of insight is a common clinical problem in psichiatric patients, but few times has been properly studied until recently. Patients with good insight tend to show a better treatment adherence with a better prognosis and swow less hostility. This study aims to investigate whether there is a relationship between the hostility degree and insight or not and to anlalyze if there are insight quantitative differences between the patients regarding their diagnoses. 168 psychotic patients were studied (including 86 patients with schizophrenia and 43 with bipolar disorder). PANNS P7 (hostility) item and G14 (poor impulse control) were analized in order to assess patients' violence and G12 in order to assess insight. All these data was correlated. It was also analyzed the PANSS results of schizophrenic vs bipolar patients regarding insight and hostility separately looking for a more homogenic pull of patients. Patients with greater hostility showed a worse impulse control and poorer insight than the rest. Schizophrenic patients showed a greater hostility and lower insight than bipolar patients. Lack of insight may lead to a greater hostility and worse impulse control. Therapeutic interventions adressed to improve insight could indirectly lower hostility and gain a better impulse control for psychotic patients. Copyright © 2010 SEP y SEPB. Published by Elsevier Espana. All rights reserved.

Unexpected Reduction of Iminoquinone and Quinone Derivatives in Positive Electrospray Ionization Mass Spectrometry and Possible Mechanism Exploration

NASA Astrophysics Data System (ADS)

Pei, Jiying; Hsu, Cheng-Chih; Zhang, Ruijie; Wang, Yinghui; Yu, Kefu; Huang, Guangming

2017-08-01

Unexpected reduction of iminoquinone (IQ) and quinone derivatives was first reported during positive electrospray ionization mass spectrometry. Upon increasing spray voltage, the intensities of IQ and quinone derivatives decreased drastically, accompanying the increase of the intensities of the reduction products, amodiaquine (AQ) and phenol derivatives. To gain more insight into the mechanism of such reduction, we explored the experimental factors that are influential to corona discharge (CD). The results show that experimental parameters that favor severe CD, including metal spray emitter, using water as spray solvent, sheath gas with low dielectric strength (e.g., nitrogen), and shorter spray tip-to-mass spectrometer inlet distance, facilitated the reduction of IQ and quinone derivatives, implying that the reduction should be closely related to CD in the gas phase. [Figure not available: see fulltext.

Plant derived edible nanoparticles as a new therapeutic approach against diseases

PubMed Central

Zhang, Mingzhen; Viennois, Emilie; Xu, Changlong; Merlin, Didier

2016-01-01

ABSTRACT In plant cells, nanoparticles containing miRNA, bioactive lipids and proteins serve as extracellular messengers to mediate cell-cell communication in a manner similar to the exosomes secreted by mammalian cells. Notably, such nanoparticles are edible. Moreover, given the proper origin and cargo, plant derived edible nanoparticles could function in interspecies communication and may serve as natural therapeutics against a variety of diseases. In addition, nanoparticles made of plant-derived lipids may be used to efficiently deliver specific drugs. Plant derived edible nanoparticles could be more easily scaled up for mass production, compared to synthetic nanoparticles. In this review, we discuss recent significant developments pertaining to plant derived edible nanoparticles and provide insight into the use of plants as a bio-renewable, sustainable, diversified platform for the production of therapeutic nanoparticles. PMID:27358751

Psychological processes in chronic pain: Influences of reward and fear learning as key mechanisms - Behavioral evidence, neural circuits, and maladaptive changes.

PubMed

Nees, Frauke; Becker, Susanne

2017-09-07

In the understanding of chronic pain, hypotheses derived from psychological theories, together with insights from physiological assessments and brain imaging, highlight the importance of mechanistically driven approaches. Physical system changes, for example following injury, can result in alterations of psychological processes and are accompanied by changes in corticolimbic circuits, which have been shown to be essential in emotional learning and memory, as well as reward processing and related behavior. In the present review, we thus highlight the importance of motivational, reward/pain relief, and fear learning processes in the context of chronic pain and discuss the potential of a mechanistic understanding of chronic pain within a clinical perspective, for example for the development of therapeutic strategies. We argue that changes in these mechanisms are not only characteristic for chronic pain, reflecting consequences of the disorder, but are also critically involved in the transition from acute to chronic pain states. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Suppression of Inflammatory Demyelinaton and Axon Degeneration through Inhibiting Kv3 Channels

PubMed Central

Jukkola, Peter; Gu, Yuanzheng; Lovett-Racke, Amy E.; Gu, Chen

2017-01-01

The development of neuroprotective and repair strategies for treating progressive multiple sclerosis (MS) requires new insights into axonal injury. 4-aminopyridine (4-AP), a blocker of voltage-gated K+ (Kv) channels, is used in symptomatic treatment of progressive MS, but the underlying mechanism remains unclear. Here we report that deleting Kv3.1—the channel with the highest 4-AP sensitivity—reduces clinical signs in experimental autoimmune encephalomyelitis (EAE), a mouse model for MS. In Kv3.1 knockout (KO) mice, EAE lesions in sensory and motor tracts of spinal cord were markedly reduced, and radial astroglia were activated with increased expression of brain derived neurotrophic factor (BDNF). Kv3.3/Kv3.1 and activated BDNF receptors were upregulated in demyelinating axons in EAE and MS lesions. In spinal cord myelin coculture, BDNF treatment promoted myelination, and neuronal firing via altering channel expression. Therefore, suppressing Kv3.1 alters neural circuit activity, which may enhance BNDF signaling and hence protect axons from inflammatory insults. PMID:29123469

“It sounds like…”: A Natural Language Processing Approach to Detecting Counselor Reflections in Motivational Interviewing

PubMed Central

Can, Doğan; Marín, Rebeca A.; Georgiou, Panayiotis G.; Imel, Zac E.; Atkins, David C.; Narayanan, Shrikanth S.

2016-01-01

The dissemination and evaluation of evidence based behavioral treatments for substance abuse problems rely on the evaluation of counselor interventions. In Motivational Interviewing (MI), a treatment that directs the therapist to utilize a particular linguistic style, proficiency is assessed via behavioral coding - a time consuming, non-technological approach. Natural language processing techniques have the potential to scale up the evaluation of behavioral treatments like MI. We present a novel computational approach to assessing components of MI, focusing on one specific counselor behavior – reflections – that are believed to be a critical MI ingredient. Using 57 sessions from 3 MI clinical trials, we automatically detected counselor reflections in a Maximum Entropy Markov Modeling framework using the raw linguistic data derived from session transcripts. We achieved 93% recall, 90% specificity, and 73% precision. Results provide insight into the linguistic information used by coders to make ratings and demonstrate the feasibility of new computational approaches to scaling up the evaluation of behavioral treatments. PMID:26784286

Reconciled rat and human metabolic networks for comparative toxicogenomics and biomarker predictions

PubMed Central

Blais, Edik M.; Rawls, Kristopher D.; Dougherty, Bonnie V.; Li, Zhuo I.; Kolling, Glynis L.; Ye, Ping; Wallqvist, Anders; Papin, Jason A.

2017-01-01

The laboratory rat has been used as a surrogate to study human biology for more than a century. Here we present the first genome-scale network reconstruction of Rattus norvegicus metabolism, iRno, and a significantly improved reconstruction of human metabolism, iHsa. These curated models comprehensively capture metabolic features known to distinguish rats from humans including vitamin C and bile acid synthesis pathways. After reconciling network differences between iRno and iHsa, we integrate toxicogenomics data from rat and human hepatocytes, to generate biomarker predictions in response to 76 drugs. We validate comparative predictions for xanthine derivatives with new experimental data and literature-based evidence delineating metabolite biomarkers unique to humans. Our results provide mechanistic insights into species-specific metabolism and facilitate the selection of biomarkers consistent with rat and human biology. These models can serve as powerful computational platforms for contextualizing experimental data and making functional predictions for clinical and basic science applications. PMID:28176778

Identification of a Druggable Pathway Controlling Glioblastoma Invasiveness.

PubMed

Pencheva, Nora; de Gooijer, Mark C; Vis, Daniel J; Wessels, Lodewyk F A; Würdinger, Tom; van Tellingen, Olaf; Bernards, René

2017-07-05

Diffuse and uncontrollable brain invasion is a hallmark of glioblastoma (GBM), but its mechanism is understood poorly. We developed a 3D ex vivo organotypic model to study GBM invasion. We demonstrate that invading GBM cells upregulate a network of extracellular matrix (ECM) components, including multiple collagens, whose expression correlates strongly with grade and clinical outcome. We identify interferon regulatory factor 3 (IRF3) as a transcriptional repressor of ECM factors and show that IRF3 acts as a suppressor of GBM invasion. Therapeutic activation of IRF3 by inhibiting casein kinase 2 (CK2)-a negative regulator of IRF3-downregulated the expression of ECM factors and suppressed GBM invasion in ex vivo and in vivo models across a panel of patient-derived GBM cell lines representative of the main molecular GBM subtypes. Our data provide mechanistic insight into the invasive capacity of GBM tumors and identify a potential therapy to inhibit GBM invasion. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Crystal structure of the μ-opioid receptor bound to a morphinan antagonist

PubMed Central

Manglik, Aashish; Kruse, Andrew C.; Kobilka, Tong Sun; Thian, Foon Sun; Mathiesen, Jesper M.; Sunahara, Roger K.; Pardo, Leonardo; Weis, William I.; Kobilka, Brian K.; Granier, Sébastien

2012-01-01

Summary Opium is one of the world’s oldest drugs, and its derivatives morphine and codeine are among the most used clinical drugs to relieve severe pain. These prototypical opioids produce analgesia as well as many of their undesirable side effects (sedation, apnea and dependence) by binding to and activating the G-protein-coupled μ-opioid receptor (μOR) in the central nervous system. Here we describe the 2.8 Å crystal structure of the μOR in complex with an irreversible morphinan antagonist. Compared to the buried binding pocket observed in most GPCRs published to date, the morphinan ligand binds deeply within a large solvent-exposed pocket. Of particular interest, the μOR crystallizes as a two-fold symmetric dimer through a four-helix bundle motif formed by transmembrane segments 5 and 6. These high-resolution insights into opioid receptor structure will enable the application of structure-based approaches to develop better drugs for the management of pain and addiction. PMID:22437502

Silibinin ameliorates anxiety/depression-like behaviors in amyloid β-treated rats by upregulating BDNF/TrkB pathway and attenuating autophagy in hippocampus.

PubMed

Song, Xiaoyu; Liu, Bo; Cui, Lingyu; Zhou, Biao; Liu, Weiwei; Xu, Fanxing; Hayashi, Toshihiko; Hattori, Shunji; Ushiki-Kaku, Yuko; Tashiro, Shin-Ichi; Ikejima, Takashi

2017-10-01

Depression is one of the most frequent psychiatric disorders of Alzheimer's disease (AD). Depression and anxiety are associated with increased risk of developing AD. Silibinin, a flavonoid derived from milk thistle (Silybum marianum), has been used as a hepato-protectant in the clinical treatment of liver diseases. In this study, the effect of silibinin on Aβ-induced anxiety/depression-like behaviors in rats was investigated. Silibinin significantly attenuated anxiety/depression-like behaviors caused by Aβ1-42-treatment as shown in tail suspension test (TST), elevated plus maze (EPM) and forced swimming tests (FST). Moreover, silibinin was able to attenuate the neuronal damage in the hippocampus of Aβ1-42-injected rats. Silibinin-treatment up-regulated the function through BDNF/TrkB pathway and attenuated autophagy in the hippocampus. Our study provides a new insight into the protective effects of silibinin in the treatment of anxiety/depression. Copyright © 2017 Elsevier Inc. All rights reserved.

Alternative research funding to improve clinical outcomes: model of prediction and prevention of sudden cardiac death.

PubMed

Myerburg, Robert J; Ullmann, Steven G

2015-04-01

Although identification and management of cardiovascular risk markers have provided important population risk insights and public health benefits, individual risk prediction remains challenging. Using sudden cardiac death risk as a base case, the complex epidemiology of sudden cardiac death risk and the substantial new funding required to study individual risk are explored. Complex epidemiology derives from the multiple subgroups having different denominators and risk profiles, while funding limitations emerge from saturation of conventional sources of research funding without foreseeable opportunities for increases. A resolution to this problem would have to emerge from new sources of funding targeted to individual risk prediction. In this analysis, we explore the possibility of a research funding strategy that would offer business incentives to the insurance industries, while providing support for unresolved research goals. The model is developed for the case of sudden cardiac death risk, but the concept is applicable to other areas of the medical enterprise. © 2015 American Heart Association, Inc.

Mesenchymal stem cells in cartilage regeneration.

PubMed

Savkovic, Vuk; Li, Hanluo; Seon, Jong-Keun; Hacker, Michael; Franz, Sandra; Simon, Jan-Christoph

2014-01-01

Articular cartilage provides life-long weight-bearing and mechanical lubrication with extraordinary biomechanical performance and simple structure. However, articular cartilage is apparently vulnerable to multifactorial damage and insufficient to self-repair, isolated in articular capsule without nerves or blood vessels. Osteoarthritis (OA) is known as a degenerative articular cartilage deficiency progressively affecting large proportion of the world population, and restoration of hyaline cartilage is clinical challenge to repair articular cartilage lesion and recreate normal functionality over long period. Mesenchymal stem cells (MSC) are highly proliferative and multipotent somatic cells that are able to differentiate mesoderm-derived cells including chondrocytes and osteoblasts. Continuous endeavors in basic research and preclinical trial have achieved promising outcomes in cartilage regeneration using MSCs. This review focuses on rationale and technologies of MSC-based hyaline cartilage repair involving tissue engineering, 3D biomaterials and growth factors. By comparing conventional treatment and current research progress, we describe insights of advantage and challenge in translation and application of MSC-based chondrogenesis for OA treatment.

Neuropeptide Substance P and the Immune Response

PubMed Central

Tehrani, Mohsen; Grace, Peter M.; Pothoulakis, Charalabos; Dana, Reza

2016-01-01

Substance P is a peptide mainly secreted by neurons and is involved in many biological processes, including nociception and inflammation. Animal models have provided insights into the biology of this peptide and offered compelling evidence for the importance of substance P in cell-to-cell communication by either paracrine or endocrine signaling. Substance P mediates interactions between neurons and immune cells, with nerve-derived substance P modulating immune cell proliferation rates and cytokine production. Intriguingly, some immune cells have also been found to secrete substance P, which hints at an integral role of substance P in the immune response. These communications play important functional roles in immunity including mobilization, proliferation and modulation of activity of immune cells. This Review summarizes current knowledge of substance P and its receptors, as well as its physiological and pathological roles. We focus on recent developments in the immuno-biology of substance P and we discuss the clinical implications of its ability to modulate the immune response. PMID:27314883

Neuropeptide substance P and the immune response.

PubMed

Mashaghi, Alireza; Marmalidou, Anna; Tehrani, Mohsen; Grace, Peter M; Pothoulakis, Charalabos; Dana, Reza

2016-11-01

Substance P is a peptide mainly secreted by neurons and is involved in many biological processes, including nociception and inflammation. Animal models have provided insights into the biology of this peptide and offered compelling evidence for the importance of substance P in cell-to-cell communication by either paracrine or endocrine signaling. Substance P mediates interactions between neurons and immune cells, with nerve-derived substance P modulating immune cell proliferation rates and cytokine production. Intriguingly, some immune cells have also been found to secrete substance P, which hints at an integral role of substance P in the immune response. These communications play important functional roles in immunity including mobilization, proliferation and modulation of the activity of immune cells. This review summarizes current knowledge of substance P and its receptors, as well as its physiological and pathological roles. We focus on recent developments in the immunobiology of substance P and discuss the clinical implications of its ability to modulate the immune response.

Horror Autoinflammaticus: The Molecular Pathophysiology of Autoinflammatory Disease*

PubMed Central

Masters, Seth L.; Simon, Anna; Aksentijevich, Ivona; Kastner, Daniel L.

2010-01-01

The autoinflammatory diseases are characterized by seemingly unprovoked episodes of inflammation, without high-titer autoantibodies or antigen-specific T cells. The concept was proposed ten years ago with the identification of the genes underlying hereditary periodic fever syndromes. This nosology has taken root because of the dramatic advances in our knowledge of the genetic basis of both mendelian and complex autoinflammatory diseases, and with the recognition that these illnesses derive from genetic variants of the innate immune system. Herein we propose an updated classification scheme based on the molecular insights garnered over the past decade, supplanting a clinical classification that has served well but is opaque to the genetic, immunologic, and therapeutic interrelationships now before us. We define six categories of autoinflammatory disease: IL-1β activation disorders (inflammasomopathies), NF-κB activation syndromes, protein misfolding disorders, complement regulatory diseases, disturbances in cytokine signaling, and macrophage activation syndromes. A system based on molecular pathophysiology will bring greater clarity to our discourse while catalyzing new hypotheses both at the bench and at the bedside. PMID:19302049

Integrative Biological Analysis For Neuropsychopharmacology

PubMed Central

Emmett, Mark R; Kroes, Roger A; Moskal, Joseph R; Conrad, Charles A; Priebe, Waldemar; Laezza, Fernanda; Meyer-Baese, Anke; Nilsson, Carol L

2014-01-01

Although advances in psychotherapy have been made in recent years, drug discovery for brain diseases such as schizophrenia and mood disorders has stagnated. The need for new biomarkers and validated therapeutic targets in the field of neuropsychopharmacology is widely unmet. The brain is the most complex part of human anatomy from the standpoint of number and types of cells, their interconnections, and circuitry. To better meet patient needs, improved methods to approach brain studies by understanding functional networks that interact with the genome are being developed. The integrated biological approaches—proteomics, transcriptomics, metabolomics, and glycomics—have a strong record in several areas of biomedicine, including neurochemistry and neuro-oncology. Published applications of an integrated approach to projects of neurological, psychiatric, and pharmacological natures are still few but show promise to provide deep biological knowledge derived from cells, animal models, and clinical materials. Future studes that yield insights based on integrated analyses promise to deliver new therapeutic targets and biomarkers for personalized medicine. PMID:23800968

Extending the Scope of GTFR Glucosylation Reactions with Tosylated Substrates for Rare Sugars Synthesis.

PubMed

Görl, Julian; Possiel, Christian; Sotriffer, Christoph; Seibel, Jürgen

2017-10-18

Functionalized rare sugars were synthesized with 2-, 3-, and 6-tosylated glucose derivatives as acceptor substrates by transglucosylation with sucrose and the glucansucrase GTFR from Streptococcus oralis. The 2- and 3-tosylated glucose derivatives yielded the corresponding 1,6-linked disaccharides (isomaltose analogues), whereas the 6-tosylated glucose derivatives resulted in 1,3-linked disaccharides (nigerose analogue) with high regioselectivity in up to 95 % yield. Docking studies provided insight into the binding mode of the acceptors and suggested two different orientations that were responsible for the change in regioselectivity. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

NCCN Guidelines® Insights Bladder Cancer, Version 2.2016 Featured Updates to the NCCN Guidelines

PubMed Central

Clark, Peter E.; Spiess, Philippe E.; Agarwal, Neeraj; Bangs, Rick; Boorjian, Stephen A.; Buyyounouski, Mark K.; Efstathiou, Jason A.; Flaig, Thomas W.; Friedlander, Terence; Greenberg, Richard E.; Guru, Khurshid A.; Hahn, Noah; Herr, Harry W.; Hoimes, Christopher; Inman, Brant A.; Kader, A. Karim; Kibel, Adam S.; Kuzel, Timothy M.; Lele, Subodh M.; Meeks, Joshua J.; Michalski, Jeff; Montgomery, Jeffrey S.; Pagliaro, Lance C.; Pal, Sumanta K.; Patterson, Anthony; Petrylak, Daniel; Plimack, Elizabeth R.; Pohar, Kamal S.; Porter, Michael P.; Sexton, Wade J.; Siefker-Radtke, Arlene O.; Sonpavde, Guru; Tward, Jonathan; Wile, Geoffrey; Dwyer, Mary A.; Smith, Courtney

2017-01-01

These NCCN Guidelines Insights discuss the major recent updates to the NCCN Guidelines for Bladder Cancer based on the review of the evidence in conjunction with the expert opinion of the panel. Recent updates include (1) refining the recommendation of intravesical bacillus Calmette-Guérin, (2) strengthening the recommendations for perioperative systemic chemotherapy, and (3) incorporating immunotherapy into second-line therapy for locally advanced or metastatic disease. These NCCN Guidelines Insights further discuss factors that affect integration of these recommendations into clinical practice. PMID:27697976

NCCN Guidelines Insights: Bladder Cancer, Version 2.2016.

PubMed

Clark, Peter E; Spiess, Philippe E; Agarwal, Neeraj; Bangs, Rick; Boorjian, Stephen A; Buyyounouski, Mark K; Efstathiou, Jason A; Flaig, Thomas W; Friedlander, Terence; Greenberg, Richard E; Guru, Khurshid A; Hahn, Noah; Herr, Harry W; Hoimes, Christopher; Inman, Brant A; Kader, A Karim; Kibel, Adam S; Kuzel, Timothy M; Lele, Subodh M; Meeks, Joshua J; Michalski, Jeff; Montgomery, Jeffrey S; Pagliaro, Lance C; Pal, Sumanta K; Patterson, Anthony; Petrylak, Daniel; Plimack, Elizabeth R; Pohar, Kamal S; Porter, Michael P; Sexton, Wade J; Siefker-Radtke, Arlene O; Sonpavde, Guru; Tward, Jonathan; Wile, Geoffrey; Dwyer, Mary A; Smith, Courtney

2016-10-01

These NCCN Guidelines Insights discuss the major recent updates to the NCCN Guidelines for Bladder Cancer based on the review of the evidence in conjunction with the expert opinion of the panel. Recent updates include (1) refining the recommendation of intravesical bacillus Calmette-Guérin, (2) strengthening the recommendations for perioperative systemic chemotherapy, and (3) incorporating immunotherapy into second-line therapy for locally advanced or metastatic disease. These NCCN Guidelines Insights further discuss factors that affect integration of these recommendations into clinical practice. Copyright © 2016 by the National Comprehensive Cancer Network.

Vibrational spectroscopic study of dehydroacetic acid and its cinnamoyl pyrone derivatives

NASA Astrophysics Data System (ADS)

Billes, Ferenc; Elečková, Lenka; Mikosch, Hans; Andruch, Vasil

2015-07-01

The infrared and Raman spectra of dehydroacetic acid and some of its derivatives were measured. The assignments of the vibrational bands were based on quantum chemical calculations and normal coordinate analysis. The optimized structures, atomic net charges and dipole moments of the investigated molecules were also results of our quantum chemical calculations. The analysis of the last properties made possible a deeper insight into the structure and substituent effect on the investigated molecules. One of them is presented in the graphical abstract.

Chromosomal rearrangement of the PAX-5 locus in lymphoplasmacytic lymphoma with t(9;14)(p13;q32).

PubMed

Iida, S; Rao, P H; Ueda, R; Chaganti, R S; Dalla-Favera, R

1999-06-01

B-cell non-Hodgkin's lymphoma (NHL) consists of heterogeneous subtypes based on histologic, immunophenotypic, and clinical findings. Recent advances in molecular biology have provided us new insights into the pathogenesis of this neoplasm at the genetic level, such as the deregulation of the protooncogenes adjoining the immunoglobulin gene (Ig) loci, which is a specific event in mature B-cell tumors. Moreover, involvement of certain protooncogenes corresponds to certain subtypes of NHL. Recently, we found that t(9;14)(p13;q32) chromosomal translocation associated with lymphoplasmacytic lymphoma (LPL) juxtaposes PAX-5 gene encoding for an essential transcription factor (BSAP: B-cell specific activator protein) for B-cell proliferation and differentiation to the Ig heavy chain gene (IgH) locus. This results in deregulated expression of the PAX-5 mRNA. We also developed a diagnostic FISH (fluorescence in situ hybridization) procedure which is able to detect 80% of the widely scattering 9p13 breakpoints involved in this translocation. Thus, an understanding of the PAX-5 gene's physiological role in B-cell development and the pathological role in tumorigenesis may lead to the optimal clinical treatment strategy for LPL and LPL-derived diffuse large cell lymphoma (DLCL).

Examining metabolic syndrome definitions in overweight Hispanic youth: a focus on insulin resistance.

PubMed

Shaibi, Gabriel Q; Goran, Michael I

2008-02-01

To examine the prevalence of the metabolic syndrome in overweight Hispanic youth according to 3 published pediatric definitions. Furthermore, the relationship of each definition to directly measured insulin resistance was examined. We conducted a secondary data analysis of 218 overweight Hispanic youth with a family history of type 2 diabetes mellitus. The metabolic syndrome was defined as >/=3 of these criteria: elevated triglyceride level, low high-density lipoprotein cholesterol level, elevated blood pressure, abdominal obesity, and hyperglycemia. The cutoff points were derived from updated definitions of Cook et al,(1) Cruz et al,(2) and Weiss et al.(3) Insulin sensitivity was determined with the insulin-modified frequently sampled intravenous glucose tolerance test. Prevalence of the metabolic syndrome ranged from 25.7% to 39%, with moderate to substantial agreement between definitions (kappa = 0.52-0.70). Regardless of definition, an inverse relationship between metabolic risk and insulin sensitivity was noted such that children with the metabolic syndrome had 51% to 60% lower insulin sensitivity compared with children without any risk factors (P

Metabolomics and Type 2 Diabetes: Translating Basic Research into Clinical Application.

PubMed

Klein, Matthias S; Shearer, Jane

2016-01-01

Type 2 diabetes (T2D) and its comorbidities have reached epidemic proportions, with more than half a billion cases expected by 2030. Metabolomics is a fairly new approach for studying metabolic changes connected to disease development and progression and for finding predictive biomarkers to enable early interventions, which are most effective against T2D and its comorbidities. In metabolomics, the abundance of a comprehensive set of small biomolecules (metabolites) is measured, thus giving insight into disease-related metabolic alterations. This review shall give an overview of basic metabolomics methods and will highlight current metabolomics research successes in the prediction and diagnosis of T2D. We summarized key metabolites changing in response to T2D. Despite large variations in predictive biomarkers, many studies have replicated elevated plasma levels of branched-chain amino acids and their derivatives, aromatic amino acids and α-hydroxybutyrate ahead of T2D manifestation. In contrast, glycine levels and lysophosphatidylcholine C18:2 are depressed in both predictive studies and with overt disease. The use of metabolomics for predicting T2D comorbidities is gaining momentum, as are our approaches for translating basic metabolomics research into clinical applications. As a result, metabolomics has the potential to enable informed decision-making in the realm of personalized medicine.

Metabolomics and Type 2 Diabetes: Translating Basic Research into Clinical Application

PubMed Central

Klein, Matthias S.; Shearer, Jane

2016-01-01

Type 2 diabetes (T2D) and its comorbidities have reached epidemic proportions, with more than half a billion cases expected by 2030. Metabolomics is a fairly new approach for studying metabolic changes connected to disease development and progression and for finding predictive biomarkers to enable early interventions, which are most effective against T2D and its comorbidities. In metabolomics, the abundance of a comprehensive set of small biomolecules (metabolites) is measured, thus giving insight into disease-related metabolic alterations. This review shall give an overview of basic metabolomics methods and will highlight current metabolomics research successes in the prediction and diagnosis of T2D. We summarized key metabolites changing in response to T2D. Despite large variations in predictive biomarkers, many studies have replicated elevated plasma levels of branched-chain amino acids and their derivatives, aromatic amino acids and α-hydroxybutyrate ahead of T2D manifestation. In contrast, glycine levels and lysophosphatidylcholine C18:2 are depressed in both predictive studies and with overt disease. The use of metabolomics for predicting T2D comorbidities is gaining momentum, as are our approaches for translating basic metabolomics research into clinical applications. As a result, metabolomics has the potential to enable informed decision-making in the realm of personalized medicine. PMID:26636104

Optimization-Based Image Reconstruction with Artifact Reduction in C-Arm CBCT

PubMed Central

Xia, Dan; Langan, David A.; Solomon, Stephen B.; Zhang, Zheng; Chen, Buxin; Lai, Hao; Sidky, Emil Y.; Pan, Xiaochuan

2016-01-01

We investigate an optimization-based reconstruction, with an emphasis on image-artifact reduction, from data collected in C-arm cone-beam computed tomography (CBCT) employed in image-guided interventional procedures. In the study, an image to be reconstructed is formulated as a solution to a convex optimization program in which a weighted data divergence is minimized subject to a constraint on the image total variation (TV); a data-derivative fidelity is introduced in the program specifically for effectively suppressing dominant, low-frequency data artifact caused by, e.g., data truncation; and the Chambolle-Pock (CP) algorithm is tailored to reconstruct an image through solving the program. Like any other reconstructions, the optimization-based reconstruction considered depends upon numerous parameters. We elucidate the parameters, illustrate their determination, and demonstrate their impact on the reconstruction. The optimization-based reconstruction, when applied to data collected from swine and patient subjects, yields images with visibly reduced artifacts in contrast to the reference reconstruction, and it also appears to exhibit a high degree of robustness against distinctively different anatomies of imaged subjects and scanning conditions of clinical significance. Knowledge and insights gained in the study may be exploited for aiding in the design of practical reconstructions of truly clinical-application utility. PMID:27694700

Optical and non-optical methods for detection and characterization of microparticles and exosomes.

PubMed

van der Pol, E; Hoekstra, A G; Sturk, A; Otto, C; van Leeuwen, T G; Nieuwland, R

2010-12-01

Microparticles and exosomes are cell-derived microvesicles present in body fluids that play a role in coagulation, inflammation, cellular homeostasis and survival, intercellular communication, and transport. Despite increasing scientific and clinical interest, no standard procedures are available for the isolation, detection and characterization of microparticles and exosomes, because their size is below the reach of conventional detection methods. Our objective is to give an overview of currently available and potentially applicable methods for optical and non-optical determination of the size, concentration, morphology, biochemical composition and cellular origin of microparticles and exosomes. The working principle of all methods is briefly discussed, as well as their applications and limitations based on the underlying physical parameters of the technique. For most methods, the expected size distribution for a given microvesicle population is determined. The explanations of the physical background and the outcomes of our calculations provide insights into the capabilities of each method and make a comparison possible between the discussed methods. In conclusion, several (combinations of) methods can detect clinically relevant properties of microparticles and exosomes. These methods should be further explored and validated by comparing measurement results so that accurate, reliable and fast solutions come within reach. © 2010 International Society on Thrombosis and Haemostasis.

Stem Cell Technology in Cardiac Regeneration: A Pluripotent Stem Cell Promise.

PubMed

Duelen, Robin; Sampaolesi, Maurilio

2017-02-01

Despite advances in cardiovascular biology and medical therapy, heart disorders are the leading cause of death worldwide. Cell-based regenerative therapies become a promising treatment for patients affected by heart failure, but also underline the need for reproducible results in preclinical and clinical studies for safety and efficacy. Enthusiasm has been tempered by poor engraftment, survival and differentiation of the injected adult stem cells. The crucial challenge is identification and selection of the most suitable stem cell type for cardiac regenerative medicine. Human pluripotent stem cells (PSCs) have emerged as attractive cell source to obtain cardiomyocytes (CMs), with potential applications, including drug discovery and toxicity screening, disease modelling and innovative cell therapies. Lessons from embryology offered important insights into the development of stem cell-derived CMs. However, the generation of a CM population, uniform in cardiac subtype, adult maturation and functional properties, is highly recommended. Moreover, hurdles regarding tumorigenesis, graft cell death, immune rejection and arrhythmogenesis need to be overcome in clinical practice. Here we highlight the recent progression in PSC technologies for the regeneration of injured heart. We review novel strategies that might overcome current obstacles in heart regenerative medicine, aiming at improving cell survival and functional integration after cell transplantation. Copyright © 2017. Published by Elsevier B.V.

Regulatory dendritic cell therapy: from rodents to clinical application.

PubMed

Raïch-Regué, Dalia; Glancy, Megan; Thomson, Angus W

2014-10-01

Dendritic cells (DC) are highly-specialized, bone marrow-derived antigen-presenting cells that induce or regulate innate and adaptive immunity. Regulatory or "tolerogenic" DC play a crucial role in maintaining self tolerance in the healthy steady-state. These regulatory innate immune cells subvert naïve or memory T cell responses by various mechanisms. Regulatory DC (DCreg) also exhibit the ability to induce or restore T cell tolerance in many animal models of autoimmune disease or transplant rejection. There is also evidence that adoptive transfer of DCreg can regulate T cell responses in non-human primates and humans. Important insights gained from in vitro studies and animal models have led recently to the development of clinical grade human DCreg, with potential to treat autoimmune disease or enhance transplant survival while reducing patient dependency on immunosuppressive drugs. Phase I trials have been conducted in type-1 diabetes and rheumatoid arthritis, with results that emphasize the feasibility and safety of DCreg therapy. This mini-review will outline how observations made using animal models have been translated into human use, and discuss the challenges faced in further developing this form of regulatory immune cell therapy in the fields of autoimmunity and transplantation. Copyright © 2013 Elsevier B.V. All rights reserved.

Optimization-based image reconstruction with artifact reduction in C-arm CBCT

NASA Astrophysics Data System (ADS)

Xia, Dan; Langan, David A.; Solomon, Stephen B.; Zhang, Zheng; Chen, Buxin; Lai, Hao; Sidky, Emil Y.; Pan, Xiaochuan

2016-10-01

We investigate an optimization-based reconstruction, with an emphasis on image-artifact reduction, from data collected in C-arm cone-beam computed tomography (CBCT) employed in image-guided interventional procedures. In the study, an image to be reconstructed is formulated as a solution to a convex optimization program in which a weighted data divergence is minimized subject to a constraint on the image total variation (TV); a data-derivative fidelity is introduced in the program specifically for effectively suppressing dominant, low-frequency data artifact caused by, e.g. data truncation; and the Chambolle-Pock (CP) algorithm is tailored to reconstruct an image through solving the program. Like any other reconstructions, the optimization-based reconstruction considered depends upon numerous parameters. We elucidate the parameters, illustrate their determination, and demonstrate their impact on the reconstruction. The optimization-based reconstruction, when applied to data collected from swine and patient subjects, yields images with visibly reduced artifacts in contrast to the reference reconstruction, and it also appears to exhibit a high degree of robustness against distinctively different anatomies of imaged subjects and scanning conditions of clinical significance. Knowledge and insights gained in the study may be exploited for aiding in the design of practical reconstructions of truly clinical-application utility.

Derivation and application of a mathematical model for long bone growth.

PubMed

Seetharam, Suneil; Bhatia, Sujata K

2012-01-01

The objective of this work was to develop a mathematical model of long bone growth and to gain insights regarding growth disorders. A cell balance (mass balance of moving cells) assessment was performed on the three regions of the growth plate, to determine the variables (including number of proliferating cells, and division rate of proliferating cells) that influence tibia growth rate. Once this relationship was established, clinical data were used to understand how tibia growth rate and number of proliferating cells change with time. These equations were then inserted into the model to determine how cell division rate changes with time. The model was utilized to determine the influence of growth time, and to measure changes in vitamin C deficiency, Indian hedgehog (IHH) expression, and bone morphogenetic protein-2 (BMP-2) implants on tibia length. According to the model, a 10-month discrepancy in growth time between the two tibias is required to produce clinically significant leg asymmetry. In addition, vitamin C deficiency, IHH overexpression, and BMP-2 implants can all affect tibia length. These bioactive molecules have the greatest effect on tibia growth rate when these perturbations occur early in life for extended periods of time. The results are significant for modeling and predicting the effects of perturbations, including bioactive implants, on long bone growth.

Low molecular weight protamine (LMWP): a nontoxic protamine substitute and an effective cell-penetrating peptide.

PubMed

He, Huining; Ye, Junxiao; Liu, Ergang; Liang, Qiuling; Liu, Quan; Yang, Victor C

2014-11-10

Low molecular weight protamine (LMWP) is a peptide fragment produced in our laboratory from enzymatic digestion of native protamine. More than 30 papers studying the properties and applications of LMWP have been published by our group in various journals since its initial discovery in 1999. Results have shown that LMWP could completely neutralize the anticoagulant functions of both heparin and low molecular weight heparin (LMWH), with reduced antigenicity and cross-reactivity toward the mice-derived anti-protamine antibodies. Aside from its potential as a heparin/LMWH antagonist, LMWP also shows the ability to retard insulin adsorption by the formation of an insoluble complex, making it a less toxic long-lasting insulin product than the conventional neutral protamine Hagedorn (NPH) insulin for diabetic control. Importantly, LMWP (Sequence: VSRRRRRRGGRRRR), with 10 arginine residues in its structure, could function as a cell-penetrating peptide (CPP), also termed protein transduction domain (PTD), to achieve effective intracellular protein or gene delivery in clinical practice. In this paper, we present a thorough review of our work related to LMWP, with the aim of providing readers an insight into its potential to be a clinical protamine substitute as well as a non-toxic cell penetrating peptide applicable to achieve intracellular protein and gene delivery. Copyright © 2014 Elsevier B.V. All rights reserved.

From the Bench to the Bedside: The Role of Semantic Web and Translational Medicine for Enabling the Next Generation Healthcare Enterprise

NASA Astrophysics Data System (ADS)

Kashyap, Vipul

The success of new innovations and technologies are very often disruptive in nature. At the same time, they enable novel next generation infrastructures and solutions. These solutions introduce great efficiencies in the form of efficient processes and the ability to create, organize, share and manage knowledge effectively; and the same time provide crucial enablers for proposing and realizing new visions. In this paper, we propose a new vision of the next generation healthcare enterprise and discuss how Translational Medicine, which aims to improve communication between the basic and clinical sciences, is a key requirement for achieving this vision. This will lead therapeutic insights may be derived from new scientific ideas - and vice versa. Translation research goes from bench to bedside, where theories emerging from preclinical experimentation are tested on disease-affected human subjects, and from bedside to bench, where information obtained from preliminary human experimentation can be used to refine our understanding of the biological principles underpinning the heterogeneity of human disease and polymorphism(s). Informatics and semantic technologies in particular, has a big role to play in making this a reality. We identify critical requirements, viz., data integration, clinical decision support and knowledge maintenance and provenance; and illustrate semantics-based solutions wrt example scenarios and use cases.

Detection of physiological changes after exercise via a remote optophysiological imaging system

NASA Astrophysics Data System (ADS)

Sun, Yu; Hu, Sijung; Azorin-Peris, Vicente; Zheng, Jia; Greenwald, Stephen; Chambers, Jonathon; Zhu, Yisheng

2011-03-01

A study of blood perfusion mapping was performed with a remote opto-physiological imaging (OPI) system coupling a sensitive CMOS camera and a custom-built resonant cavity light emitting diode (RCLED) ringlight. The setup is suitable for the remote assessment of blood perfusion in tissue over a wide range of anatomical locations. The purpose of this study is to evaluate the reliability and stability of the OPI system when measuring a cardiovascular variable of clinical interest, in this case, heart rate. To this end, the non-contact and contact photoplethysmographic (PPG) signals obtained from the OPI system and conventional PPG sensor were recorded simultaneously from each of 12 subjects before and after 5-min of cycling exercise. The time-frequency representation (TFR) method was used to visualize the time-dependent behavior of the signal frequency. The physiological parameters derived from the images captured by the OPI system exhibit comparable functional characteristics to those taken from conventional contact PPG pulse waveform measurements in both the time and frequency domains. Finally and more importantly, a previously developed opto-physiological model was employed to provide a 3-D representation of blood perfusion in human tissue which could provide a new insight into clinical assessment and diagnosis of circulatory pathology in various tissue segments.

Deriving simple empirical relationships between aerodynamic and optical aerosol measurements and their application

USDA-ARS?s Scientific Manuscript database

Different measurement techniques for aerosol characterization and quantification either directly or indirectly measure different aerosol properties (i.e. count, mass, speciation, etc.). Comparisons and combinations of multiple measurement techniques sampling the same aerosol can provide insight into...

Paleomagnetic investigations at Mahd adh Dhahab, Kingdom of Saudi Arabia

USGS Publications Warehouse

Gettings, M.E.

1985-01-01

The results of this work suggest that more extensive paleomagnetic investigations of the felsic volcanic and volcanic-derived rocks of the northern Arabian shield should provide greater insight into the structural evolution of the shield, and these investigations are recommended.

Behavioral Design Teams: The Next Frontier in Clinical Delivery Innovation?

PubMed

Robertson, Ted; Darling, Matthew; Leifer, Jennifer; Footer, Owen; Gordski, Dani

2017-11-01

A deep understanding of human behavior is critical to designing effective health care delivery models, tools, and processes. Currently, however, few mechanisms exist to systematically apply insights about human behavior to improve health outcomes. Behavioral design teams (BDTs) are a successful model for applying behavioral insights within an organization. Already operational within government, this model can be adapted to function in a health care setting. To explore how BDTs could be applied to clinical care delivery and review models for integrating these teams within health care organizations. Interviews with experts in clinical delivery innovation and applied behavioral science, as well as leaders of existing government BDTs. BDTs are most effective when they enjoy top-level executive support, are co-led by a domain expert and behavioral scientist, collaborate closely with key staff and departments, have access to data and IT support, and operate a portfolio of projects. BDTs could be embedded in health care organizations in multiple ways, including in or just below the CEO’s office, within a quality improvement unit, or within an internal innovation center. When running a portfolio, BDTs achieve a greater number and diversity of insights at lower costs. They also become a platform for strategic learning and scaling.

Learning Clinical Skills during Bedside Teaching Encounters in General Practice: A Video-Observational Study with Insights from Activity Theory

ERIC Educational Resources Information Center

Ajjawi, Rola; Rees, Charlotte; Monrouxe, Lynn V.

2015-01-01

Purpose: This paper aims to explore how opportunities for learning clinical skills are negotiated within bedside teaching encounters (BTEs). Bedside teaching, within the medical workplace, is considered essential for helping students develop their clinical skills. Design/methodology/approach: An audio and/or video observational study examining…

"Ultimately, mom has the call": Viewing clinical trial decision making among patients with ovarian cancer through the lens of relational autonomy.

PubMed

Asiedu, Gladys B; Ridgeway, Jennifer L; Carroll, Katherine; Jatoi, Aminah; Radecki Breitkopf, Carmen

2018-04-14

This study employs the concept of relational autonomy to understand how relational encounters with family members (FMs) and care providers may shape decisions around ovarian cancer patients' clinical trial (CT) participation. The study also offers unique insights into how FMs view patients' decision making. In-depth interviews were conducted with 33 patients with ovarian cancer who had been offered a CT and 39 FMs. Data were inductively analysed using a thematic approach and deductively informed by constructs derived from the theory of relational autonomy (RA). Patients' relationships, experiences and social status were significant resources that shaped their decisions. Patients did not give equal weight to all relationships and created boundaries around whom to include in decision making. Doctors' recommendations and perceived enthusiasm were described as influential in CT decisions. Both patients with ovarian cancer and their FMs maintained that patients have the "final say," indicating an individualistic autonomy. However, maintaining the "final say" in the decision-making process is constitutive of patients' relationships, emphasizing a relational approach to autonomy. FMs support patients' autonomy and they do so particularly when they believe the patient is capable of making the right choices. Although ethical principles underlying informed consent for CT participation emphasize individual autonomy, greater attention to relational autonomy is warranted for a more comprehensive understanding of CT decision making. © 2018 Mayo Clinic. Health Expectations published by John Wiley & Sons Ltd.

Attacking the Multi-tiered Proteolytic Pathology of COPD: New Insights from Basic and Translational Studies

PubMed Central

Djekic, Uros V; Gaggar, Amit; Weathington, Nathaniel M

2015-01-01

Protease activity in inflammation is complex. Proteases released by cells in response to infection, cytokines, or environmental triggers like cigarette smoking cause breakdown of the extracellular matrix (ECM). In chronic inflammatory diseases like chronic obstructive pulmonary disease (COPD), current findings indicate that pathology and morbidity are driven by dysregulation of protease activity, either through hyperactivity of proteases or deficiency or dysfunction their antiprotease regulators. Animal studies demonstrate the accuracy of this hypothesis through genetic and pharmacologic tools. New work shows that ECM destruction generates peptide fragments active on leukocytes via neutrophil or macrophage chemotaxis towards collagen and elastin derived peptides respectively. Such fragments now have been isolated and characterized in vivo in each case. Collectively, this describes a biochemical circuit in which protease activity leads to activation of local immunocytes, which in turn release cytokines and more proteases, leading to further leukocyte infiltration and cyclical disease progression that is chronic. This circuit concept is well known, and is intrinsic to the protease-antiprotease hypothesis; recently analytic techniques have become sensitive enough to establish fundamental mechanisms of this hypothesis, and basic and clinical data now implicate protease activity and peptide signaling as pathologically significant pharmacologic targets. This review discusses targeting protease activity for chronic inflammatory disease with special attention to COPD, covering important basic and clinical findings in the field; novel therapeutic strategies in animal or human studies; and a perspective on the successes and failures of agents with a focus on clinical potential in human disease. PMID:19026684

100 Years Later: Celebrating the Contributions of X-ray Crystallography to Allergy and Clinical Immunology

PubMed Central

Pomés, Anna; Chruszcz, Maksymilian; Gustchina, Alla; Minor, Wladek; Mueller, Geoffrey A.; Pedersen, Lars C.; Wlodawer, Alexander; Chapman, Martin D.

2015-01-01

Current knowledge of molecules involved in immunology and allergic disease results from significant contributions of X-ray crystallography, a discipline that just celebrated its 100th anniversary. The histories of allergens and X-ray crystallography are intimately intertwined. The first enzyme structure to be determined was lysozyme, also known as the chicken food allergen Gal d 4. Crystallography determines the exact three-dimensional positions of atoms in molecules. Structures of molecular complexes in the disciplines of immunology and allergy have revealed the atoms involved in molecular interactions and in mechanisms of disease. These complexes include peptides presented by MHC class II molecules, cytokines bound to their receptors, allergen-antibody complexes, and innate immune receptors with their ligands. The information derived from crystallographic studies provides insights into the function of molecules. Allergen function is one of the determinants of environmental exposure, which is essential for IgE sensitization. Proteolytic activity of allergens or their capacity to bind lipopolysaccharides may also contribute to allergenicity. The atomic positions define the molecular surface that is accessible to antibodies. This surface in turn determines antibody specificity and cross-reactivity that are important factors for the selection of allergen panels used for molecular diagnosis and for the interpretation of clinical symptoms. This review celebrates the contributions of X-ray crystallography to clinical immunology and allergy, focusing on new molecular perspectives that influence the diagnosis and treatment of allergic diseases. PMID:26145985

100 Years later: Celebrating the contributions of x-ray crystallography to allergy and clinical immunology.

PubMed

Pomés, Anna; Chruszcz, Maksymilian; Gustchina, Alla; Minor, Wladek; Mueller, Geoffrey A; Pedersen, Lars C; Wlodawer, Alexander; Chapman, Martin D

2015-07-01

Current knowledge of molecules involved in immunology and allergic disease results from the significant contributions of x-ray crystallography, a discipline that just celebrated its 100th anniversary. The histories of allergens and x-ray crystallography are intimately intertwined. The first enzyme structure to be determined was lysozyme, also known as the chicken food allergen Gal d 4. Crystallography determines the exact 3-dimensional positions of atoms in molecules. Structures of molecular complexes in the disciplines of immunology and allergy have revealed the atoms involved in molecular interactions and mechanisms of disease. These complexes include peptides presented by MHC class II molecules, cytokines bound to their receptors, allergen-antibody complexes, and innate immune receptors with their ligands. The information derived from crystallographic studies provides insights into the function of molecules. Allergen function is one of the determinants of environmental exposure, which is essential for IgE sensitization. Proteolytic activity of allergens or their capacity to bind LPSs can also contribute to allergenicity. The atomic positions define the molecular surface that is accessible to antibodies. In turn, this surface determines antibody specificity and cross-reactivity, which are important factors for the selection of allergen panels used for molecular diagnosis and the interpretation of clinical symptoms. This review celebrates the contributions of x-ray crystallography to clinical immunology and allergy, focusing on new molecular perspectives that influence the diagnosis and treatment of allergic diseases. Copyright © 2015 American Academy of Allergy, Asthma & Immunology. All rights reserved.

Osteogenesis imperfecta: Clinical diagnosis, nomenclature and severity assessment

PubMed Central

Van Dijk, FS; Sillence, DO

2014-01-01

Recently, the genetic heterogeneity in osteogenesis imperfecta (OI), proposed in 1979 by Sillence et al., has been confirmed with molecular genetic studies. At present, 17 genetic causes of OI and closely related disorders have been identified and it is expected that more will follow. Unlike most reviews that have been published in the last decade on the genetic causes and biochemical processes leading to OI, this review focuses on the clinical classification of OI and elaborates on the newly proposed OI classification from 2010, which returned to a descriptive and numerical grouping of five OI syndromic groups. The new OI nomenclature and the pre-and postnatal severity assessment introduced in this review, emphasize the importance of phenotyping in order to diagnose, classify, and assess severity of OI. This will provide patients and their families with insight into the probable course of the disorder and it will allow physicians to evaluate the effect of therapy. A careful clinical description in combination with knowledge of the specific molecular genetic cause is the starting point for development and assessment of therapy in patients with heritable disorders including OI. © 2014 The Authors. American Journal of Medical Genetics Published by Wiley Periodicals, Inc. This is an open access article under the terms of the Creative Commons Attribution–NonCommercial–NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. PMID:24715559

Practice of Clinical Supervision.

ERIC Educational Resources Information Center

Holland, Patricia E.

1988-01-01

Clinical supervision remained grounded in empirical inquiry as late as Morris Cogan's writings on the subject in 1973. With the acknowledgment of Thomas Kuhn's (1962) paradigm shift, educational theory and practice developed interpretive methodologies. An interpretive reflection on Cogan's rationale offers insights into the current, matured…

Gaining Insights on Nasopharyngeal Carcinoma Treatment Outcome Using Clinical Data Mining Techniques.

PubMed

Ghaibeh, A Ammar; Kasem, Asem; Ng, Xun Jin; Nair, Hema Latha Krishna; Hirose, Jun; Thiruchelvam, Vinesh

2018-01-01

The analysis of Electronic Health Records (EHRs) is attracting a lot of research attention in the medical informatics domain. Hospitals and medical institutes started to use data mining techniques to gain new insights from the massive amounts of data that can be made available through EHRs. Researchers in the medical field have often used descriptive statistics and classical statistical methods to prove assumed medical hypotheses. However, discovering new insights from large amounts of data solely based on experts' observations is difficult. Using data mining techniques and visualizations, practitioners can find hidden knowledge, identify interesting patterns, or formulate new hypotheses to be further investigated. This paper describes a work in progress on using data mining methods to analyze clinical data of Nasopharyngeal Carcinoma (NPC) cancer patients. NPC is the fifth most common cancer among Malaysians, and the data analyzed in this study was collected from three states in Malaysia (Kuala Lumpur, Sabah and Sarawak), and is considered to be the largest up-to-date dataset of its kind. This research is addressing the issue of cancer recurrence after the completion of radiotherapy and chemotherapy treatment. We describe the procedure, problems, and insights gained during the process.

Cognitive function and competitive employment in schizophrenia: relative contribution of insight and psychopathology.

PubMed

Giugiario, Michela; Crivelli, Barbara; Mingrone, Cinzia; Montemagni, Cristiana; Scalese, Mara; Sigaudo, Monica; Rocca, Giuseppe; Rocca, Paola

2012-04-01

This study investigated the relationships among insight, psychopathology, cognitive function, and competitive employment in order to determine whether insight and/or psychopathology carried the influence of cognitive function to competitive employment. We recruited 253 outpatients with stable schizophrenia and we further divided our sample into two groups of patients (unemployed and competitive employment subjects). Clinical and neuropsychological assessments were performed. All clinical variables significantly different between the two groups of subjects were subsequently analyzed using a binary logistic regression to assess their independent contribution to competitive employment in the two patients' groups. On the basis of the regression results two mediation analyses were performed. Verbal memory, general psychopathology, and awareness of mental illness were significantly associated with competitive employment in our sample. Both awareness of mental illness and general psychopathology had a role in mediating the verbal memory-competitive employment relationship. Taken together, these findings confirmed the importance of cognitive function in obtaining competitive employment. Our results also highlighted the independent role of general psychopathology and awareness of illness on occupational functioning in schizophrenia. Thus, a greater attention must be given to the systematic investigation of insight and general psychopathology in light of an amelioration of vocational functioning in stable schizophrenia.

Breathing and Relaxation

MedlinePlus

... Programs Health Information Doctors & Departments Clinical Research & Science Education & Training Home Health Insights Stress & Relaxation Breathing and Relaxation Breathing and Relaxation Make ...

Correlates of insight into different symptom dimensions in obsessive-compulsive disorder.

PubMed

Fontenelle, Jùlia M; Harrison, Ben J; Santana, Lívia; Conceição do Rosário, Maria; Versiani, Marcio; Fontenelle, Leonardo F

2013-02-01

In this study, we evaluated insight into different obsessive-compulsive disorder (OCD) symptom dimensions and their impact on clinical and sociodemographic features of patients with OCD. Sixty OCD patients were assessed with the Brown Assessment of Beliefs Scale (BABS), the Dimensional Yale-Brown Obsessive-Compulsive Scale-Short Version, the Beck Depression Inventory, and the Sheehan Disability Scale. Two methods of using BABS were employed: 1) a traditional approach, which considers a composite of the insight into existing OCD symptoms, and 2) an alternative approach, which includes assessments of insight into each OCD symptom dimension separately. Composite BABS scores correlated with global severity of OCD and depressive symptoms, and degree of interference on social life/leisure activities and family life/home responsibilities. Dimension-specific correlations between severity of symptoms and insight ranged from very high (P = .87, for hoarding) to moderate (P = .61, for miscellaneous symptoms). Greater severity of depression and concomitant generalized anxiety disorder were independently associated with lower levels of insight into aggressive/checking symptoms. While earlier-onset OCD was associated with lower insight into sexual/religious and symmetry symptoms, later-onset OCD displayed lower insight into hoarding. Assessing insight into dimension-specific OCD symptoms may challenge the existence of clear-cut OCD with fair or poor insight.

Contributions of treatment theory and enablement theory to rehabilitation research and practice.

PubMed

Whyte, John

2014-01-01

Scientific theory is crucial to the advancement of clinical research. The breadth of rehabilitation treatment requires that many different theoretical perspectives be incorporated into the design and testing of treatment interventions. In this article, the 2 broad classes of theory relevant to rehabilitation research and practice are defined, and their distinct but complementary contributions to research and clinical practice are explored. These theory classes are referred to as treatment theories (theories about how to effect change in clinical targets) and enablement theories (theories about how changes in a proximal clinical target will influence distal clinical aims). Treatment theories provide the tools for inducing clinical change but do not specify how far reaching the ultimate impact of the change will be. Enablement theories model the impact of changes on other areas of function but provide no insight as to how treatment can create functional change. Treatment theories are more critical in the early stages of treatment development, whereas enablement theories become increasingly relevant in specifying the clinical significance and practical effectiveness of more mature treatments. Understanding the differences in the questions these theory classes address and how to combine their insights is crucial for effective research development and clinical practice. Copyright © 2014 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

Navigating complexity to breed disease-resistant crops

USDA-ARS?s Scientific Manuscript database

Crop losses due to disease constitute a burden to global food security and agricultural sustainability. The use of genetic resistance is an environmentally-friendly way to reduce these losses. This paper considers the insights derived from various lines of research on disease resistance and manageme...

Lithospheric Structure from Mars Global Surveyor Topography and Gravity and Implications for the Early Thermal Evolution of Mars

NASA Technical Reports Server (NTRS)

Solomon, Sean C.; Zuber, Maria T.; Phillips, Roger J.; Smith, David E.; Tyler, G. Leonard; Aharonson, Oded; Balmino, Georges; Banerdt, W. B.; Head, James W.; Johnson, Catherine L.

2000-01-01

Regional variations in the thickness of the elastic lithosphere on Mars derived from a combined analysis of topography and gravity anomalies determined by Mars Global Surveyor provide new insight into the planet's thermal history.

Are Higher Education Institutions Prepared for Learning Analytics?

ERIC Educational Resources Information Center

Ifenthaler, Dirk

2017-01-01

Higher education institutions and involved stakeholders can derive multiple benefits from learning analytics by using different data analytics strategies to produce summative, real-time, and predictive insights and recommendations. However, are institutions and academic as well as administrative staff prepared for learning analytics? A learning…

Face-to-Face versus Distance Learning: Psychological Consequences and Practical Implications.

ERIC Educational Resources Information Center

Kahl, Thomas N.; Cropley, Arthur J.

1986-01-01

Summarizes differences between face-to-face and distance learners at Fernuniversitat (West Germany) in terms of demographics, motivation, study conditions, and personal consequences, in order to provide some empirically derived insights into the psychological consequences of distance learning for learners. (MBR)

Generating community-built tools for data sharing and analysis in environmental networks

USGS Publications Warehouse

Read, Jordan S.; Gries, Corinna; Read, Emily K.; Klug, Jennifer; Hanson, Paul C.; Hipsey, Matthew R.; Jennings, Eleanor; O'Reilley, Catherine; Winslow, Luke A.; Pierson, Don; McBride, Christopher G.; Hamilton, David

2016-01-01

Rapid data growth in many environmental sectors has necessitated tools to manage and analyze these data. The development of tools often lags behind the proliferation of data, however, which may slow exploratory opportunities and scientific progress. The Global Lake Ecological Observatory Network (GLEON) collaborative model supports an efficient and comprehensive data–analysis–insight life cycle, including implementations of data quality control checks, statistical calculations/derivations, models, and data visualizations. These tools are community-built and openly shared. We discuss the network structure that enables tool development and a culture of sharing, leading to optimized output from limited resources. Specifically, data sharing and a flat collaborative structure encourage the development of tools that enable scientific insights from these data. Here we provide a cross-section of scientific advances derived from global-scale analyses in GLEON. We document enhancements to science capabilities made possible by the development of analytical tools and highlight opportunities to expand this framework to benefit other environmental networks.

Large-scale modeled contemporary and future water temperature estimates for 10774 Midwestern U.S. Lakes

USGS Publications Warehouse

Winslow, Luke A.; Hansen, Gretchen J. A.; Read, Jordan S.; Notaro, Michael

2017-01-01

Climate change has already influenced lake temperatures globally, but understanding future change is challenging. The response of lakes to changing climate drivers is complex due to the nature of lake-atmosphere coupling, ice cover, and stratification. To better understand the diversity of lake responses to climate change and give managers insight on individual lakes, we modelled daily water temperature profiles for 10,774 lakes in Michigan, Minnesota, and Wisconsin for contemporary (1979–2015) and future (2020–2040 and 2080–2100) time periods with climate models based on the Representative Concentration Pathway 8.5, the worst-case emission scenario. In addition to lake-specific daily simulated temperatures, we derived commonly used, ecologically relevant annual metrics of thermal conditions for each lake. We include all supporting lake-specific model parameters, meteorological drivers, and archived code for the model and derived metric calculations. This unique dataset offers landscape-level insight into the impact of climate change on lakes.

Large-scale modeled contemporary and future water temperature estimates for 10774 Midwestern U.S. Lakes

PubMed Central

Winslow, Luke A.; Hansen, Gretchen J.A.; Read, Jordan S; Notaro, Michael

2017-01-01

Climate change has already influenced lake temperatures globally, but understanding future change is challenging. The response of lakes to changing climate drivers is complex due to the nature of lake-atmosphere coupling, ice cover, and stratification. To better understand the diversity of lake responses to climate change and give managers insight on individual lakes, we modelled daily water temperature profiles for 10,774 lakes in Michigan, Minnesota, and Wisconsin for contemporary (1979–2015) and future (2020–2040 and 2080–2100) time periods with climate models based on the Representative Concentration Pathway 8.5, the worst-case emission scenario. In addition to lake-specific daily simulated temperatures, we derived commonly used, ecologically relevant annual metrics of thermal conditions for each lake. We include all supporting lake-specific model parameters, meteorological drivers, and archived code for the model and derived metric calculations. This unique dataset offers landscape-level insight into the impact of climate change on lakes. PMID:28440790

Insights into the chicken IgY with emphasis on the generation and applications of chicken recombinant monoclonal antibodies.

PubMed

Lee, Warren; Syed Atif, Ali; Tan, Soo Choon; Leow, Chiuan Herng

2017-08-01

The advantages of chicken (Gallus gallus domesticus) antibodies as immunodiagnostic and immunotherapeutic biomolecules has only been recently recognized. Even so, chicken antibodies remain less-well characterized than their mammalian counterparts. This review aims at providing a current overview of the structure, function, development and generation of chicken antibodies. Additionally, brief but comprehensive insights into current knowledge pertaining to the immunogenetic framework and diversity-generation of the chicken immunoglobulin repertoire which have contributed to the establishment of recombinant chicken mAb-generating methods are discussed. Focus is provided on the current methods used to generate antibodies from chickens with added emphasis on the generation of recombinant chicken mAbs and its derivative formats. The advantages and limitations of established protocols for the generation of chicken mAbs are highlighted. The various applications of recombinant chicken mAbs and its derivative formats in immunodiagnostics and immunotherapy are further detailed. Copyright © 2017 Elsevier B.V. All rights reserved.

Large-scale modeled contemporary and future water temperature estimates for 10774 Midwestern U.S. Lakes

NASA Astrophysics Data System (ADS)

Winslow, Luke A.; Hansen, Gretchen J. A.; Read, Jordan S.; Notaro, Michael

2017-04-01

Climate change has already influenced lake temperatures globally, but understanding future change is challenging. The response of lakes to changing climate drivers is complex due to the nature of lake-atmosphere coupling, ice cover, and stratification. To better understand the diversity of lake responses to climate change and give managers insight on individual lakes, we modelled daily water temperature profiles for 10,774 lakes in Michigan, Minnesota, and Wisconsin for contemporary (1979-2015) and future (2020-2040 and 2080-2100) time periods with climate models based on the Representative Concentration Pathway 8.5, the worst-case emission scenario. In addition to lake-specific daily simulated temperatures, we derived commonly used, ecologically relevant annual metrics of thermal conditions for each lake. We include all supporting lake-specific model parameters, meteorological drivers, and archived code for the model and derived metric calculations. This unique dataset offers landscape-level insight into the impact of climate change on lakes.

When VSEPR Fails: Experimental and Theoretical Investigations of the Behavior of Alkaline-Earth-Metal Acetylides

PubMed Central

Guino-o, Marites A.; Alexander, Jacob S.; McKee, Michael L.; Hope, Håkon; Englich, Ulrich B.

2014-01-01

The synthesis, structural, and spectral characterization as well as a theoretical study of a family of alkaline-earth-metal acetylides provides insights into synthetic access and the structural and bonding characteristics of this group of highly reactive compounds. Based on our earlier communication that reported unusual geometry for a family of triphenylsilyl-substituted alkaline-earth-metal acetylides, we herein present our studies on an expanded family of target derivatives, providing experimental and theoretical data to offer new insights into the intensively debated theme of structural chemistry in heavy alkaline-earth-metal chemistry. PMID:19844925

Development of hydrophilic interaction chromatography with quadruple time-of-flight mass spectrometry for heparin and low molecular weight heparin disaccharide analysis.

PubMed

Ouyang, Yilan; Wu, Chengling; Sun, Xue; Liu, Jianfen; Linhardt, Robert J; Zhang, Zhenqing

2016-01-30

Heparin and low molecular weight heparin (LMWH) are widely used as clinical anticoagulants. The determination of their composition and structural heterogeneity still challenges analysts. Disaccharide compositional analysis, utilizing heparinase-catalyzed depolymerization, is one of the most important ways to evaluate the sequence, structural composition and quality of heparin and LMWH. Hydrophilic interaction chromatography coupled with quadruple time-of-flight mass spectrometry (HILIC/QTOFMS) has been developed to analyze the resulting digestion products. HILIC shows good resolution and excellent MS compatibility. Digestion products of heparin and LMWHs afforded up to 16 compounds that were separated using HILIC and analyzed semi-quantitatively. These included eight common disaccharides, two disaccharides derived from chain termini, three 3-O-sulfo-group-containing tetrasaccharides, along with three linkage region tetrasaccharides and their derivatives. Structures of these digestion products were confirmed by mass spectral analysis. The disaccharide compositions of a heparin, two batches of the LMWH, enoxaparin, and two batches of the LMWH, nadroparin, were compared. In addition to identifying disaccharides, 3-O-sulfo-group-containing tetrasaccharides, linkage region tetrasaccharides were observed having slightly different compositions and contents in these heparin products suggesting that they had been prepared using different starting materials or production processes. Thus, compositional analysis using HILIC/QTOFMS offers a unique insight into different heparin products. Copyright © 2015 John Wiley & Sons, Ltd.

Antigen-Specific Th17 Cells Are Primed by Distinct and Complementary Dendritic Cell Subsets in Oropharyngeal Candidiasis

PubMed Central

Kirchner, Florian R.; Becattini, Simone; Rülicke, Thomas; Sallusto, Federica; LeibundGut-Landmann, Salomé

2015-01-01

Candida spp. can cause severe and chronic mucocutaneous and systemic infections in immunocompromised individuals. Protection from mucocutaneous candidiasis depends on T helper cells, in particular those secreting IL-17. The events regulating T cell activation and differentiation toward effector fates in response to fungal invasion in different tissues are poorly understood. Here we generated a Candida-specific TCR transgenic mouse reactive to a novel endogenous antigen that is conserved in multiple distant species of Candida, including the clinically highly relevant C. albicans and C. glabrata. Using TCR transgenic T cells in combination with an experimental model of oropharyngeal candidiasis (OPC) we investigated antigen presentation and Th17 priming by different subsets of dendritic cells (DCs) present in the infected oral mucosa. Candida-derived endogenous antigen accesses the draining lymph nodes and is directly presented by migratory DCs. Tissue-resident Flt3L-dependent DCs and CCR2-dependent monocyte-derived DCs collaborate in antigen presentation and T cell priming during OPC. In contrast, Langerhans cells, which are also present in the oral mucosa and have been shown to prime Th17 cells in the skin, are not required for induction of the Candida-specific T cell response upon oral challenge. This highlights the functional compartmentalization of specific DC subsets in different tissues. These data provide important new insights to our understanding of tissue-specific antifungal immunity. PMID:26431538

Regulatory Myeloid Cells in Transplantation

PubMed Central

Rosborough, Brian R.; Raïch-Regué, Dàlia; Turnquist, Heth R.; Thomson, Angus W.

2013-01-01

Regulatory myeloid cells (RMC) are emerging as novel targets for immunosuppressive (IS) agents and hold considerable promise as cellular therapeutic agents. Herein, we discuss the ability of regulatory macrophages (Mreg), regulatory dendritic cells (DCreg) and myeloid-derived suppressor cells (MDSC) to regulate alloimmunity, their potential as cellular therapeutic agents and the IS agents that target their function. We consider protocols for the generation of RMC and the selection of donor- or recipient-derived cells for adoptive cell therapy. Additionally, the issues of cell trafficking and antigen (Ag) specificity following RMC transfer are discussed. Improved understanding of the immunobiology of these cells has increased the possibility of moving RMC into the clinic to reduce the burden of current IS agents and promote Ag-specific tolerance. In the second half of this review, we discuss the influence of established and experimental IS agents on myeloid cell populations. IS agents believed historically to act primarily on T cell activation and proliferation are emerging as important regulators of RMC function. Better insights into the influence of IS agents on RMC will enhance our ability to develop cell therapy protocols to promote the function of these cells. Moreover, novel IS agents may be designed to target RMC in situ to promote Ag-specific immune regulation in transplantation and usher in a new era of immune modulation exploiting cells of myeloid origin. PMID:24092382

Proteomics in Forensic Sciences: Identification of the Nature of the Last Meal at Autopsy.

PubMed

Pieri, Maria; Lombardi, Antonio; Basilicata, Pascale; Mamone, Gianfranco; Picariello, Gianluca

2018-06-13

A long-term psychiatric 40 years-old male patient was found dead at 9:00 a.m. in the clinic where he lived. Death was caused by traumatic injuries, which the sanitary staff imputed to a fall. Nurses declared that the patient refused having breakfast, whereas at autopsy the stomach contained 350 g of whitish semifluid material. Using both shotgun and gel-based proteomics, we demonstrated that the chyme contained partly digested milk- and bread-derived proteins, eaten during a recent breakfast. The conflict between evidence and assertions of the attending sanitary staff prompted the Legal Authority to undertake detailed investigations to ascertain facts and possible responsibilities. The herein characterization provides insights in the in vivo mechanisms of gastric breakdown of food proteins in a real meal. β-lactoglobulin was partially resistant to gastric digestion as confirmed by Western blot analysis, in contrast to caseins and wheat gluten proteins, which had been degraded by gastric fluids. In addition to a complex pattern of gastric proteins (e.g., mucin-5AC, pepsin A-3, pepsinogen C, gastric lipase, gastrokine-2, trefoil factors), chyme contained intact proteins and variably sized food-derived polypeptides arising from peptic and nonpeptic proteolytic cleavage as well as heterodimeric disulfide-cross-linked peptides. These findings suggest that the current analytical workflows offer only a partial picture of the real complexity of the human "digestome".

[Insight in schizophrenia: relationship to family history, and positive and negative symptoms].

PubMed

Danki, Demet; Dilbaz, Nesrin; Okay, Ihsan Tuncer; Telci, Sükran

2007-01-01

To determine the level of insight among patients with schizophrenia and to compare sociodemographic and clinical features. The study included 66 patients with schizophrenia based on DSM-IV criteria. A semi-structured sociodemographic instrument, the Positive and Negative Syndrome Scale (PANSS), and the Schedule for Assessing the Three Components of Insight (SATCI) were used for the study. Family history was significantly related to low-level insight in schizophrenic patients. Positive symptom scores in patients with a family history of schizophrenia were significantly higher than in patients without such a family history. Positive and general psychopathological symptoms were inversely related to level of insight in patients with schizophrenia. There was no significant relationship between the negative symptoms scores and level of insight. Family history of schizophrenia in schizophrenic patients was significantly related to low-level insight. Insight in the schizophrenic patients was affected by biological, psychological, and psychosociological factors. Family history of schizophrenia was one of these factors, which may affect the level of insight in numerous ways. Studies of patient family position and its relationship to insight have generally explored the effects of family situation on schizophrenia and insight, but not family history and its relationship to insight. In this study positive symptom severity was higher in patients with a family history of schizophrenia than in those without such a history. There was a positive relationship between low-level insight and both high positive and general psychopathology symptom levels in patients with schizophrenia.

The effects of aging on insight into illness in schizophrenia: a review†

PubMed Central

Gerretsen, Philip; Plitman, Eric; Rajji, Tarek K.; Graff-Guerrero, Ariel

2015-01-01

Objectives Impaired insight into illness is a prevalent feature of schizophrenia, which negatively influences treatment adherence and clinical outcomes. Little is known about the effects of aging on insight impairment. We aimed to review the available research literature on the effects of aging on insight into illness in schizophrenia, in relation to positive, negative, and cognitive symptoms. Ultimately, we propose a trajectory of insight in schizophrenia across the lifespan. Method A systematic Medline® literature search was conducted, searching for English language studies describing the relationship of insight into illness in schizophrenia with aging. Results We identified 62 studies. Insight impairment is associated with illness severity, premorbid intellectual function (i.e. IQ), executive function, and memory. Insight impairment improves modestly during midlife, worsening again in late life. It tends to fluctuate with each episode of psychosis, likely in relation to worsening positive symptoms that improve with antipsychotic treatment. The relationship between insight impairment and cognitive dysfunction appears to attenuate with age, while the relationship with lower premorbid intellectual function is preserved. The association between impaired insight and negative symptoms is unclear. Conclusions The available literature suggests that the course of insight impairment follows a U-shaped curve, where insight impairment is severe during the first episode of psychosis, modestly improves over midlife, and declines again in late life. Future studies are required to investigate the trajectory of insight into illness and its core domains across the lifespan from prodromal phase to late life. PMID:25055980

Compressive mechanical characterization of non-human primate spinal cord white matter.

PubMed

Jannesar, Shervin; Allen, Mark; Mills, Sarah; Gibbons, Anne; Bresnahan, Jacqueline C; Salegio, Ernesto A; Sparrey, Carolyn J

2018-05-02

The goal of developing computational models of spinal cord injury (SCI) is to better understand the human injury condition. However, finite element models of human SCI have used rodent spinal cord tissue properties due to a lack of experimental data. Central nervous system tissues in non human primates (NHP) closely resemble that of humans and therefore, it is expected that material constitutive models obtained from NHPs will increase the fidelity and the accuracy of human SCI models. Human SCI most often results from compressive loading and spinal cord white matter properties affect FE predicted patterns of injury; therefore, the objectives of this study were to characterize the unconfined compressive response of NHP spinal cord white matter and present an experimentally derived, finite element tractable constitutive model for the tissue. Cervical spinal cords were harvested from nine male adult NHPs (Macaca mulatta). White matter biopsy samples (3 mm in diameter) were taken from both lateral columns of the spinal cord and were divided into four strain rate groups for unconfined dynamic compression and stress relaxation (post-mortem <1-hour). The NHP spinal cord white matter compressive response was sensitive to strain rate and showed substantial stress relaxation confirming the viscoelastic behavior of the material. An Ogden 1st order model best captured the non-linear behavior of NHP white matter in a quasi-linear viscoelastic material model with 4-term Prony series. This study is the first to characterize NHP spinal cord white matter at high (>10/sec) strain rates typical of traumatic injury. The finite element derived material constitutive model of this study will increase the fidelity of SCI computational models and provide important insights for transferring pre-clinical findings to clinical treatments. Spinal cord injury (SCI) finite element (FE) models provide an important tool to bridge the gap between animal studies and human injury, assess injury prevention technologies (e.g. helmets, seatbelts), and provide insight into the mechanisms of injury. Although, FE model outcomes depend on the assumed material constitutive model, there is limited experimental data for fresh spinal cords and all was obtained from rodent, porcine or bovine tissues. Central nervous system tissues in non human primates (NHP) more closely resemble humans. This study characterizes fresh NHP spinal cord material properties at high strains rates and large deformations typical of SCI for the first time. A constitutive model was defined that can be readily implemented in finite strain FE analysis of SCI. Copyright © 2018. Published by Elsevier Ltd.

Free radical-mediated systemic immunity in plants.

PubMed

Wendehenne, David; Gao, Qing-Ming; Kachroo, Aardra; Kachroo, Pradeep

2014-08-01

Systemic acquired resistance (SAR) is a form of defense that protects plants against a broad-spectrum of secondary infections by related or unrelated pathogens. SAR related research has witnessed considerable progress in recent years and a number of chemical signals and proteins contributing to SAR have been identified. All of these diverse constituents share their requirement for the phytohormone salicylic acid, an essential downstream component of the SAR pathway. However, recent work demonstrating the essential parallel functioning of nitric oxide (NO)-derived and reactive oxygen species (ROS)-derived signaling together with SA provides important new insights in the overlapping pathways leading to SAR. This review discusses the potential significance of branched pathways and the relative contributions of NO/ROS-derived and SA-derived pathways in SAR. Copyright © 2014 Elsevier Ltd. All rights reserved.

Production of biorenewable styrene: utilization of biomass-derived sugars and insights into toxicity.

PubMed

Lian, Jieni; McKenna, Rebekah; Rover, Marjorie R; Nielsen, David R; Wen, Zhiyou; Jarboe, Laura R

2016-05-01

Fermentative production of styrene from glucose has been previously demonstrated in Escherichia coli. Here, we demonstrate the production of styrene from the sugars derived from lignocellulosic biomass depolymerized by fast pyrolysis. A previously engineered styrene-producing strain was further engineered for utilization of the anhydrosugar levoglucosan via expression of levoglucosan kinase. The resulting strain produced 240 ± 3 mg L(-1) styrene from pure levoglucosan, similar to the 251 ± 3 mg L(-1) produced from glucose. When provided at a concentration of 5 g L(-1), pyrolytic sugars supported styrene production at titers similar to those from pure sugars, demonstrating the feasibility of producing this important industrial chemical from biomass-derived sugars. However, the toxicity of contaminant compounds in the biomass-derived sugars and styrene itself limit further gains in production. Styrene toxicity is generally believed to be due to membrane damage. Contrary to this prevailing wisdom, our quantitative assessment during challenge with up to 200 mg L(-1) of exogenously provided styrene showed little change in membrane integrity; membrane disruption was observed only during styrene production. Membrane fluidity was also quantified during styrene production, but no changes were observed relative to the non-producing control strain. This observation that styrene production is much more damaging to the membrane integrity than challenge with exogenously supplied styrene provides insight into the mechanism of styrene toxicity and emphasizes the importance of verifying proposed toxicity mechanisms during production instead of relying upon results obtained during exogenous challenge.

Neuronopathic Lysosomal Storage Diseases: Clinical and Pathologic Findings

ERIC Educational Resources Information Center

Prada, Carlos E.; Grabowski, Gregory A.

2013-01-01

Background: The lysosomal--autophagocytic system diseases (LASDs) affect multiple body systems including the central nervous system (CNS). The progressive CNS pathology has its onset at different ages, leading to neurodegeneration and early death. Methods: Literature review provided insight into the current clinical neurological findings,…

Neurocounseling: Brain-Based Clinical Approaches

ERIC Educational Resources Information Center

Field, Thomas A., Ed.; Jones, Laura K., Ed.; Russell-Chapin, Lori A.

2017-01-01

This text presents current, accessible information on enhancing the counseling process using a brain-based paradigm. Leading experts provide guidelines and insights for becoming a skillful neuroscience-informed counselor, making direct connections between the material covered and clinical practice. In this much-needed resource-the first to address…

Researching asthma across the ages: insights from the National Heart, Lung, and Blood Institute's Asthma Network.

PubMed

Cabana, Michael D; Kunselman, Susan J; Nyenhuis, Sharmilee M; Wechsler, Michael E

2014-01-01

Clinical asthma studies across different age groups (ie, cross-age studies) can potentially offer insight into the similarities, differences, and relationships between childhood and adult asthma. The National Institutes of Health's Asthma Research Network (AsthmaNet) is unique and innovative in that it has merged pediatric and adult asthma research into a single clinical research network. This combination enhances scientific exchange between pediatric and adult asthma investigators and encourages the application of cross-age studies that involve participants from multiple age groups who are generally not studied together. The experience from AsthmaNet in the development of cross-age protocols highlights some of the issues in the evaluation of cross-age research in asthma. The aim of this review is to summarize these challenges, including the selection of parallel cross-age clinical interventions, identification of appropriate controls, measurement of meaningful clinical outcomes, and various ethical and logistic issues. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

Depot-medication compliance for patients with psychotic disorders: the importance of illness insight and treatment motivation.

PubMed

Noordraven, Ernst L; Wierdsma, André I; Blanken, Peter; Bloemendaal, Anthony Ft; Mulder, Cornelis L

2016-01-01

Noncompliance is a major problem for patients with a psychotic disorder. Two important risk factors for noncompliance that have a severe negative impact on treatment outcomes are impaired illness insight and lack of motivation. Our cross-sectional study explored how they are related to each other and their compliance with depot medication. Interviews were conducted in 169 outpatients with a psychotic disorder taking depot medication. Four patient groups were defined based on low or high illness insight and on low or high motivation. The associations between depot-medication compliance, motivation, and insight were illustrated using generalized linear models. Generalized linear model showed a significant interaction effect between motivation and insight. Patients with poor insight and high motivation for treatment were more compliant (94%) (95% confidence interval [CI]: 1.821, 3.489) with their depot medication than patients with poor insight and low motivation (61%) (95% CI: 0.288, 0.615). Patients with both insight and high motivation for treatment were less compliant (73%) (95% CI: 0.719, 1.315) than those with poor insight and high motivation. Motivation for treatment was more strongly associated with depot-medication compliance than with illness insight. Being motivated to take medication, whether to get better or for other reasons, may be a more important factor than having illness insight in terms of improving depot-medication compliance. Possible implications for clinical practice are discussed.

Insight in schizophrenia: from conceptualization to neuroscience.

PubMed

Ouzir, Mounir; Azorin, Jean Michel; Adida, Marc; Boussaoud, Driss; Battas, Omar

2012-04-01

Lack of insight into illness is a prevalent and distinguishing feature of schizophrenia, which has a complex history and has been given a variety of definitions. Currently, insight is measured and treated as a multidimensional phenomenon, because it is believed to result from psychological, neuropsychological and organic factors. Thus, schizophrenia patients may display dramatic disorders including demoralization, depression and a higher risk of suicide, all of which are directly or indirectly related to a lack of insight into their illness, and make the treatment difficult. To improve the treatment of people with schizophrenia, it is thus crucial to advance research on insight into their illness. Insight is studied in a variety of ways. Studies may focus on the relationship between insight and psychopathology, may view behavioral outcomes or look discretely at the cognitive dysfunction versus anatomy level of insight. All have merit but they are dispersed across a wide body of literature and rarely are the findings integrated and synthesized in a meaningful way. The aim of this study was to synthesize findings across the large body of literature dealing with insight, to highlight its multidimensional nature, measurement, neuropsychology and social impact in schizophrenia. The extensive literature on the cognitive consequences of lack of insight and the contribution of neuroimaging techniques to elucidating neurological etiology of insight deficits, is also reviewed. © 2012 The Authors. Psychiatry and Clinical Neurosciences © 2012 Japanese Society of Psychiatry and Neurology.

Cognitive insight in psychosis: the relationship between self-certainty and self-reflection dimensions and neuropsychological measures.

PubMed

Cooke, Michael A; Peters, Emmanuelle R; Fannon, Dominic; Aasen, Ingrid; Kuipers, Elizabeth; Kumari, Veena

2010-07-30

Cognitive insight in schizophrenia encompasses the evaluation and reinterpretation of distorted beliefs and appraisals. We investigated the neuropsychological basis of cognitive insight in psychosis. It was predicted that, like clinical insight, cognitive insight would be associated with a wide range of neuropsychological functions, but would be most strongly associated with measures of executive function. Sixty-five outpatients with schizophrenia or schizoaffective disorder were assessed on tests of intelligence quotient (IQ), executive function, verbal fluency, attention and memory, and completed the Beck Cognitive Insight Scale, which includes two subscales, self-certainty and self-reflection. Higher self-certainty scores reflect greater certainty about being right and more resistant to correction (poor insight), while higher self-reflection scores indicate the expression of introspection and the willingness to acknowledge fallibility (good insight). The self-certainty dimension of poor cognitive insight was significantly associated with lower scores on the Behavioural Assessment of Dysexecutive Syndrome; this relationship was not mediated by IQ. There were no relationships between self-reflection and any neuropsychological measures. We conclude that greater self-certainty (poor cognitive insight) is modestly associated with poorer executive function in psychotic individuals; self-reflection has no association with executive function. The self-certainty and self-reflection dimensions of cognitive insight have differential correlates, and probably different mechanisms, in psychosis. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

Macrophages discriminate glycosylation patterns of apoptotic cell-derived microparticles.

PubMed

Bilyy, Rostyslav O; Shkandina, Tanya; Tomin, Andriy; Muñoz, Luis E; Franz, Sandra; Antonyuk, Volodymyr; Kit, Yuriy Ya; Zirngibl, Matthias; Fürnrohr, Barbara G; Janko, Christina; Lauber, Kirsten; Schiller, Martin; Schett, Georg; Stoika, Rostyslav S; Herrmann, Martin

2012-01-02

Inappropriate clearance of apoptotic remnants is considered to be the primary cause of systemic autoimmune diseases, like systemic lupus erythematosus. Here we demonstrate that apoptotic cells release distinct types of subcellular membranous particles (scMP) derived from the endoplasmic reticulum (ER) or the plasma membrane. Both types of scMP exhibit desialylated glycotopes resulting from surface exposure of immature ER-derived glycoproteins or from surface-borne sialidase activity, respectively. Sialidase activity is activated by caspase-dependent mechanisms during apoptosis. Cleavage of sialidase Neu1 by caspase 3 was shown to be directly involved in apoptosis-related increase of surface sialidase activity. ER-derived blebs possess immature mannosidic glycoepitopes and are prioritized by macrophages during clearance. Plasma membrane-derived blebs contain nuclear chromatin (DNA and histones) but not components of the nuclear envelope. Existence of two immunologically distinct types of apoptotic blebs may provide new insights into clearance-related diseases.

The evolution of insight, paranoia and depression during early schizophrenia.

PubMed

Drake, R J; Pickles, A; Bentall, R P; Kinderman, P; Haddock, G; Tarrier, N; Lewis, S W

2004-02-01

How insight, paranoia and depression evolve in relation to each other during and after the first episode of schizophrenia is poorly understood but of clinical importance. Serial assessments over 18 months were made using multiple instruments in a consecutive sample of 257 patients with first episode DSM-IV non-affective psychosis. Repeated measures of paranoia, insight, depression and self-esteem were analysed using structural equation modelling, to examine the direction of relationships over time after controlling for confounds. Depression was predicted directly by greater insight, particularly at baseline, and by greater paranoia at every stage of follow-up. Neither relationship was mediated by self-esteem, although there was a weak association of lower self-esteem with greater depression and better insight. Paranoia was not strongly associated with insight. Duration of untreated psychosis and substance use at baseline predicted depression at 18 months. In first-episode psychosis, good insight predicts depression. Subsequently, paranoia is the strongest predictor. Neither effect is mediated by low self-esteem. Effective treatment of positive symptoms is important in preventing and treating low mood in early schizophrenia.

On data processing required to derive mobility patterns from passively-generated mobile phone data

PubMed Central

Wang, Feilong; Chen, Cynthia

2018-01-01

Passively-generated mobile phone data is emerging as a potential data source for transportation research and applications. Despite the large amount of studies based on the mobile phone data, only a few have reported the properties of such data, and documented how they have processed the data. In this paper, we describe two types of common mobile phone data: Call Details Record (CDR) data and sightings data, and propose a data processing framework and the associated algorithms to address two key issues associated with the sightings data: locational uncertainty and oscillation. We show the effectiveness of our proposed methods in addressing these two issues compared to the state of art algorithms in the field. We also demonstrate that without proper processing applied to the data, the statistical regularity of human mobility patterns—a key, significant trait identified for human mobility—is over-estimated. We hope this study will stimulate more studies in examining the properties of such data and developing methods to address them. Though not as glamorous as those directly deriving insights on mobility patterns (such as statistical regularity), understanding properties of such data and developing methods to address them is a fundamental research topic on which important insights are derived on mobility patterns. PMID:29398790

Insights from Human/Mouse genome comparisons

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pennacchio, Len A.

2003-03-30

Large-scale public genomic sequencing efforts have provided a wealth of vertebrate sequence data poised to provide insights into mammalian biology. These include deep genomic sequence coverage of human, mouse, rat, zebrafish, and two pufferfish (Fugu rubripes and Tetraodon nigroviridis) (Aparicio et al. 2002; Lander et al. 2001; Venter et al. 2001; Waterston et al. 2002). In addition, a high-priority has been placed on determining the genomic sequence of chimpanzee, dog, cow, frog, and chicken (Boguski 2002). While only recently available, whole genome sequence data have provided the unique opportunity to globally compare complete genome contents. Furthermore, the shared evolutionary ancestrymore » of vertebrate species has allowed the development of comparative genomic approaches to identify ancient conserved sequences with functionality. Accordingly, this review focuses on the initial comparison of available mammalian genomes and describes various insights derived from such analysis.« less

Insight and suicidality in first-episode psychosis: understanding the influence of suicidal history on insight dimensions at first presentation.

PubMed

López-Moríñigo, Javier D; Wiffen, Benjamin; O'Connor, Jennifer; Dutta, Rina; Di Forti, Marta; Murray, Robin M; David, Anthony S

2014-05-01

Lack of insight is a cardinal feature of psychosis with crucial implications for outcome. Concerns have been raised regarding a link between insight and suicidality. This study aimed to test the relationship between suicidal behaviour preceding first-episode psychosis (FEP) and insight dimensions at treatment onset. A total of 112 FEP inpatients were recruited. Suicidal events prior to admission were recorded. Insight was assessed multidimensionally with the Schedule for the Assessment of Insight - Expanded version shortly after admission. Suicidal and non-suicidal patients were compared regarding scores on 'total insight' and three insight domains: 'awareness of mental illness', 'relabeling of psychotic experiences as abnormal' and 'compliance'. This analysis was also adjusted for a set of sociodemographic, clinical, neurocognitive and psychopathological variables. Bivariate analyses demonstrated a direct association between previous suicidality and all insight domains. However, these associations did not survive multivariable regression models, which demonstrated gender (female), shorter duration of untreated psychosis (DUP) and psychopathological symptoms - depression and disorganization - to mediate the influence of suicidal history on insight, and therefore to underlie the latter. Insight dimensions in FEP patients are influenced by having suicidal antecedents through some mediating variables such as gender, DUP and depression. Further prospective studies are needed to clarify the potential implications of these findings on the management of insight in FEP. As suicidal history is associated with greater levels of both depression and insight at first presentation, these three variables might be useful in predicting further suicidal events. © 2013 Wiley Publishing Asia Pty Ltd.

Upstream factors affecting Tualatin River algae—Tracking the 2008 Anabaena algae bloom to Wapato Lake, Oregon

USGS Publications Warehouse

Rounds, Stewart A.; Carpenter, Kurt D.; Fesler, Kristel J.; Dorsey, Jessica L.

2015-12-17

The results and insights derived from this study can be used to enhance future monitoring and data collection strategies designed to improve water quality and plankton models and better predict dissolved-oxygen concentrations in the lower Tualatin River.

Lattice Truss Structural Response Using Energy Methods

NASA Technical Reports Server (NTRS)

Kenner, Winfred Scottson

1996-01-01

A deterministic methodology is presented for developing closed-form deflection equations for two-dimensional and three-dimensional lattice structures. Four types of lattice structures are studied: beams, plates, shells and soft lattices. Castigliano's second theorem, which entails the total strain energy of a structure, is utilized to generate highly accurate results. Derived deflection equations provide new insight into the bending and shear behavior of the four types of lattices, in contrast to classic solutions of similar structures. Lattice derivations utilizing kinetic energy are also presented, and used to examine the free vibration response of simple lattice structures. Derivations utilizing finite element theory for unique lattice behavior are also presented and validated using the finite element analysis code EAL.

Drug-eluting stents. Insights from invasive imaging technologies.

PubMed

Honda, Yasuhiro

2009-08-01

Drug-eluting stents (DES) represent a revolutionary technology in their unique ability to provide both mechanical and biological solutions simultaneously to the target lesion. As a result of biological effects from the pharmacological agents and interaction of DES components with the arterial wall, considerable differences exist between DES and conventional bare metal stents (BMS), yet some of the old lessons learned in the BMS era remain clinically significant. In this context, contrast angiography provides very little information about in vivo device properties and their biomechanical effects on the arterial wall. In contrast, current catheter-based imaging tools, such as intravascular ultrasound, optical coherence tomography, and intracoronary angioscopy can offer unique insights into DES through direct assessment of the device and treated vessel in the clinical setting. This article reviews these insights from current DES with particular focus on performance and safety characteristics as well as discussing an optimal deployment technique, based upon findings obtained through the use of the invasive imaging technologies.

Parents of adolescents with psychiatric disorders: insight into the disorder, self-stigma and parental stress.

PubMed

Hasson-Ohayon, Ilanit; Tuval-Mashiach, Rivka; Morag-Yaffe, Mayad; Gaziel, Meyrav; Schapir, Lior; Zalsman, Gil; Shoval, Gal

2014-07-01

Parents of adolescents with mental disorders experience stress partially due to the way they perceive and experience their offspring's disorder. The current study assessed the mediator role of self-stigma in the relationship between insight into the disorder and parental stress of parents of adolescents with mental disorders. A total of 37 parents of adolescents with psychiatric disorders were assessed for their level of insight, self-stigma and parental stress. The hypothesized mediation model was confirmed and is consistent with previous study on parents of adults with severe mental illness. The positive association between insight and parental stress is mediated by these parents' self-stigma, suggesting that insight increases the self-stigma, which in turn increases the parental stress. These results may have clinical implications with regard to the treatment of the family of adolescents with mental disorders. Copyright © 2014 Elsevier Inc. All rights reserved.

Psychiatrists' accounts of insight.

PubMed

Galasinski, Dariusz; Opalinski, Konrad

2012-11-01

Our main aim was to examine how insight into schizophrenia is discursively represented in psychiatrists' accounts, how these accounts relate to the current psychiatric literature on insight, and their potential clinical consequences. The article is anchored in the constructionist view of discourse and is based on nine semistructured interviews with specialist psychiatrists. We discuss three dimensions of insight into schizophrenia in the data we collected: a sense of illness, criticism, and readiness to receive treatment. We argue that they are embodiments of the dominant medical perspective in the relations between patients and physicians. Whereas in the former two it is possessing and accepting psychiatric knowledge which constitutes having insight, in the latter it is unquestioning acceptance and trust in whatever treatment the doctor deems fit to administer. We conclude with a discussion of medicalization of experience of mental illness, which appears to be the preferred mode of patient narrative for psychiatrists.

Proteogenomics | Office of Cancer Clinical Proteomics Research

Cancer.gov

Proteogenomics, or the integration of proteomics with genomics and transcriptomics, is an emerging approach that promises to advance basic, translational and clinical research.  By combining genomic and proteomic information, leading scientists are gaining new insights due to a more complete and unified understanding of complex biological processes.

Special Issue on Clinical Supervision: A Reflection

ERIC Educational Resources Information Center

Bernard, Janine M.

2010-01-01

This special issue about clinical supervision offers an array of contributions with disparate insights into the supervision process. Using a synergy of supervision model, the articles are categorized as addressing the infrastructure required for adequate supervision, the relationship dynamics endemic to supervision, or the process of delivering…

Genomics of Systemic Lupus Erythematosus: Insights Gained by Studying Monogenic Young-Onset Systemic Lupus Erythematosus.

PubMed

Hiraki, Linda T; Silverman, Earl D

2017-08-01

Systemic lupus erythematosus (SLE) is a systemic, autoimmune, multisystem disease with a heterogeneous clinical phenotype. Genome-wide association studies have identified multiple susceptibility loci, but these explain a fraction of the estimated heritability. This is partly because within the broad spectrum of SLE are monogenic diseases that tend to cluster in patients with young age of onset, and in families. This article highlights insights into the pathogenesis of SLE provided by these monogenic diseases. It examines genetic causes of complement deficiency, abnormal interferon production, and abnormalities of tolerance, resulting in monogenic SLE with overlapping clinical features, autoantibodies, and shared inflammatory pathways. Copyright © 2017 Elsevier Inc. All rights reserved.

Relationship between cognitive insight and attenuated delusional symptoms in individuals with at-risk mental state.

PubMed

Uchida, Tomohiro; Matsumoto, Kazunori; Ito, Fumiaki; Ohmuro, Noriyuki; Miyakoshi, Tetsuo; Ueno, Takashi; Matsuoka, Hiroo

2014-06-30

Cognitive insight, defined as the ability to evaluate and correct one׳s own distorted beliefs and misinterpretations, is hypothesized to contribute to the development of psychotic symptoms. We investigated cognitive insight in individuals with at-risk mental state (ARMS), which is associated with a clinically high risk of psychosis. Sixty individuals with ARMS were compared with 200 healthy controls in terms of cognitive insight measured using the Beck Cognitive Insight Scale. We also investigated the relationship between cognitive insight and attenuated delusional symptoms. In addition, we examined differences in the cognitive insight of individuals with ARMS with or without near-threshold delusional symptoms and differences in the cognitive insight of individuals with ARMS with or without later transition to psychosis. The results showed that individuals with ARMS exhibited higher self-certainty than healthy controls, indicating impairments in cognitive insight in the former. More importantly, our results revealed that self-certainty was correlated with attenuated delusional symptoms and that individuals with ARMS who had near threshold delusional symptoms had higher self-certainty. These findings indicate that overconfidence in one׳s own beliefs or judgments might be related to the formation and maintenance of attenuated delusions in individuals with ARMS. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Contextualized perceptions of movement as a source of expanded insight: People with multiple sclerosis' experience with physiotherapy.

PubMed

Normann, Britt; Sørgaard, Knut W; Salvesen, Rolf; Moe, Siri

2013-01-01

The hospitals' outpatient clinics for people with multiple sclerosis (PwMS) are important in the health care. Research regarding physiotherapy in such clinics is limited. The purpose was to investigate how PwMS perceive movement during single sessions of physiotherapy in a hospital's outpatient clinic, and what do these experiences mean for the patient's insight into their movement disturbances? Qualitative research interviews were performed with a purposive sample of 12 PwMS and supplemented with seven videotaped sessions. Content analysis was performed. The results indicate that contextualized perceptions of movement appear to be an essential source for PwMS to gain expanded insight with regard to their individual movement disturbances regardless of their ambulatory status. The contextualization implies that perceptions of movement are integrated with the physiotherapist's explanations regarding optimizing gait and balance or other activities of daily life. Perceptions of improvement in body part movement and/or functional activities are vital to enhancing their understanding of their individual movement disorders, and they may provide expanded insight regarding future possibilities and limitations involving everyday tasks. The implementation of movements, which transforms the perceived improvement into self-assisted exercises, appeared to be meaningful. Contextualized perceptions of improvements in movement may strengthen the person's sense of ownership and sense of agency and thus promote autonomy and self-encouragement. The findings underpin the importance of contextualized perceptions of movement based on exploration of potential for change, as an integrated part of information and communication in the health care for PwMS. Further investigations are necessary to deepen our knowledge.

Epigenetic deregulation in chronic lymphocytic leukemia: Clinical and biological impact.

PubMed

Mansouri, Larry; Wierzbinska, Justyna Anna; Plass, Christoph; Rosenquist, Richard

2018-02-07

Deregulated transcriptional control caused by aberrant DNA methylation and/or histone modifications is a hallmark of cancer cells. In chronic lymphocytic leukemia (CLL), the most common adult leukemia, the epigenetic 'landscape' has added a new layer of complexity to our understanding of this clinically and biologically heterogeneous disease. Early studies identified aberrant DNA methylation, often based on single gene promoter analysis with both biological and clinical impact. Subsequent genome-wide profiling studies revealed differential DNA methylation between CLLs and controls and in prognostics subgroups of the disease. From these studies, it became apparent that DNA methylation in regions outside of promoters, such as enhancers, is important for the regulation of coding genes as well as for the regulation of non-coding RNAs. Although DNA methylation profiles are reportedly stable over time and in relation to therapy, a higher epigenetic heterogeneity or 'burden' is seen in more aggressive CLL subgroups, albeit as non-recurrent 'passenger' events. More recently, DNA methylation profiles in CLL analyzed in relation to differentiating normal B-cell populations revealed that the majority of the CLL epigenome reflects the epigenomes present in the cell of origin and that only a small fraction of the epigenetic alterations represents truly CLL-specific changes. Furthermore, CLL patients can be grouped into at least three clinically relevant epigenetic subgroups, potentially originating from different cells at various stages of differentiation and associated with distinct outcomes. In this review, we summarize the current understanding of the DNA methylome in CLL, the role of histone modifying enzymes, highlight insights derived from animal models and attempts made to target epigenetic regulators in CLL along with the future directions of this rapidly advancing field. Copyright © 2018 Elsevier Ltd. All rights reserved.

High dose hydrocortisone immediately after trauma may alter the trajectory of PTSD: interplay between clinical and animal studies.

PubMed

Zohar, Joseph; Yahalom, Hila; Kozlovsky, Nitsan; Cwikel-Hamzany, Shlomit; Matar, Michael A; Kaplan, Zeev; Yehuda, Rachel; Cohen, Hagit

2011-11-01

High-dose corticosteroids have been reported to reduce symptoms of acute stress and post-traumatic stress in polytrauma patients and in animal studies. The underlying mechanism of action remains largely unclear. These issues were addressed in parallel in the clinical and preclinical studies below. In this preliminary study, 25 patients with acute stress symptoms were administered a single intravenous bolus of high-dose hydrocortisone (100-140 mg) or placebo within 6 h of a traumatic event in a prospective, randomized, double-blind, placebo-controlled pilot study. Early single high-dose hydrocortisone intervention attenuated the core symptoms of both the acute stress and of subsequent PTSD in patients. High-dose hydrocortisone treatment given in the first few hours after a traumatic experience was associated with significant favorable changes in the trajectory of exposure to trauma, as expressed by the reduced risk of the development of PTSD post-trauma. In parallel, a comparative study of morphological arborization in dentate gyrus and its modulating molecules was performed in stress-exposed animals treated with high-dose hydrocortisone. Steroid-treated stressed animals displayed significantly increased dendritic growth and spine density, with increased levels of brain-derived neurotrophic factor (BDNF) and obtunded postsynaptic density-95 (PSD-95) levels. The animal study provided insights into the potential mechanism of this intervention, as it identified relevant morphological and biochemical associations to the clinical observations. Thus, evidence from clinical and animal studies suggests that there is a "window of opportunity" in the early aftermath of trauma to help those who are vulnerable to the development of chronic PTSD. Copyright © 2011 Elsevier B.V. and ECNP. All rights reserved.

Mutations associated with reduced surotomycin susceptibility in Clostridium difficile and Enterococcus species.

PubMed

Adams, Hannah M; Li, Xiang; Mascio, Carmela; Chesnel, Laurent; Palmer, Kelli L

2015-07-01

Clostridium difficile infection (CDI) is an urgent public health concern causing considerable clinical and economic burdens. CDI can be treated with antibiotics, but recurrence of the disease following successful treatment of the initial episode often occurs. Surotomycin is a rapidly bactericidal cyclic lipopeptide antibiotic that is in clinical trials for CDI treatment and that has demonstrated superiority over vancomycin in preventing CDI relapse. Surotomycin is a structural analogue of the membrane-active antibiotic daptomycin. Previously, we utilized in vitro serial passage experiments to derive C. difficile strains with reduced surotomycin susceptibilities. The parent strains used included ATCC 700057 and clinical isolates from the restriction endonuclease analysis (REA) groups BI and K. Serial passage experiments were also performed with vancomycin-resistant and vancomycin-susceptible Enterococcus faecium and Enterococcus faecalis. The goal of this study is to identify mutations associated with reduced surotomycin susceptibility in C. difficile and enterococci. Illumina sequence data generated for the parent strains and serial passage isolates were compared. We identified nonsynonymous mutations in genes coding for cardiolipin synthase in C. difficile ATCC 700057, enoyl-(acyl carrier protein) reductase II (FabK) and cell division protein FtsH2 in C. difficile REA type BI, and a PadR family transcriptional regulator in C. difficile REA type K. Among the 4 enterococcal strain pairs, 20 mutations were identified, and those mutations overlap those associated with daptomycin resistance. These data give insight into the mechanism of action of surotomycin against C. difficile, possible mechanisms for resistance emergence during clinical use, and the potential impacts of surotomycin therapy on intestinal enterococci. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Insights in spatio-temporal characterization of human fetal neural stem cells.

PubMed

Martín-Ibáñez, Raquel; Guardia, Inés; Pardo, Mónica; Herranz, Cristina; Zietlow, Rike; Vinh, Ngoc-Nga; Rosser, Anne; Canals, Josep M

2017-05-01

Primary human fetal cells have been used in clinical trials of cell replacement therapy for the treatment of neurodegenerative disorders such as Huntington's disease (HD). However, human fetal primary cells are scarce and difficult to work with and so a renewable source of cells is sought. Human fetal neural stem cells (hfNSCs) can be generated from human fetal tissue, but little is known about the differences between hfNSCs obtained from different developmental stages and brain areas. In the present work we characterized hfNSCs, grown as neurospheres, obtained from three developmental stages: 4-5, 6-7 and 8-9weeks post conception (wpc) and four brain areas: forebrain, cortex, whole ganglionic eminence (WGE) and cerebellum. We observed that, as fetal brain development proceeds, the number of neural precursors is diminished and post-mitotic cells are increased. In turn, primary cells obtained from older embryos are more sensitive to the dissociation process, their viability is diminished and they present lower proliferation ratios compared to younger embryos. However, independently of the developmental stage of derivation proliferation ratios were very low in all cases. Improvements in the expansion rates were achieved by mechanical, instead of enzymatic, dissociation of neurospheres but not by changes in the seeding densities. Regardless of the developmental stage, neurosphere cultures presented large variability in the viability and proliferation rates during the initial 3-4 passages, but stabilized achieving significant expansion rates at passage 5 to 6. This was true also for all brain regions except cerebellar derived cultures that did not expand. Interestingly, the brain region of hfNSC derivation influences the expansion potential, being forebrain, cortex and WGE derived cells the most expandable compared to cerebellar. Short term expansion partially compromised the regional identity of cortical but not WGE cultures. Nevertheless, both expanded cultures were multipotent and kept the ability to differentiate to region specific mature neuronal phenotypes. Copyright © 2017 Elsevier Inc. All rights reserved.

Fostering new relational experience: clinical process in couple psychotherapy.

PubMed

Marmarosh, Cheri L

2014-03-01

One of the most critical goals for couple psychotherapy is to foster a new relational experience in the session where the couple feels safe enough to reveal more vulnerable emotions and to explore their defensive withdrawal, aggressive attacking, or blaming. The lived intimate experience in the session offers the couple an opportunity to gain integrative insight into their feelings, expectations, and behaviors that ultimately hinder intimacy. The clinical processes that are necessary include empathizing with the couple and facilitating safety within the session, looking for opportunities to explore emotions, ruptures, and unconscious motivations that maintain distance in the relationship, and creating a new relational experience in the session that has the potential to engender integrative insight. These clinical processes will be presented with empirical support. Experts from a session will be used to highlight how these processes influence the couple and promote increased intimacy. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

Clinical biomarkers of angiogenesis inhibition

PubMed Central

Brown, Aaron P.; Citrin, Deborah E.; Camphausen, Kevin A.

2009-01-01

Introduction An expanding understanding of the importance of angiogenesis in oncology and the development of numerous angiogenesis inhibitors are driving the search for biomarkers of angiogenesis. We review currently available candidate biomarkers and surrogate markers of anti-angiogenic agent effect. Discussion A number of invasive, minimally invasive, and non-invasive tools are described with their potential benefits and limitations. Diverse markers can evaluate tumor tissue or biological fluids, or specialized imaging modalities. Conclusions The inclusion of these markers into clinical trials may provide insight into appropriate dosing for desired biological effects, appropriate timing of additional therapy, prediction of individual response to an agent, insight into the interaction of chemotherapy and radiation following exposure to these agents, and perhaps most importantly, a better understanding of the complex nature of angiogenesis in human tumors. While many markers have potential for clinical use, it is not yet clear which marker or combination of markers will prove most useful. PMID:18414993

Progesterone signaling mediated through progesterone receptor membrane component-1 in ovarian cells with special emphasis on ovarian cancer.

PubMed

Peluso, John J

2011-08-01

Various ovarian cell types including granulosa cells and ovarian surface epithelial cells express the progesterone (P4) binding protein, progesterone receptor membrane component-1 (PGRMC1). PGRMC1 is also expressed in ovarian tumors. PGRMC1 plays an essential role in promoting the survival of both normal and cancerous ovarian cell in vitro. Given the clinical significance of factors that regulate the viability of ovarian cancer, this review will focus on the role of PGRMC1 in ovarian cancer, while drawing insights into the mechanism of PGRMC1's action from cell lines derived from healthy ovaries as well as ovarian tumors. Studies using PGRMC1siRNA demonstrated that P4's ability to inhibit ovarian cells from undergoing apoptosis in vitro is dependent on PGRMC1. To confirm the importance of PGRMC1, the ability of PGRMC1-deplete ovarian cancer cell lines to form tumors in intact nude mice was assessed. Compared to PGRMC1-expressing ovarian cancer cells, PGRMC1-deplete ovarian cancer cells formed tumors in fewer mice (80% compared to 100% for controls). Moreover, the number of tumors derived from PGRMC1-deplete ovarian cancer cells was 50% of that observed in controls. Finally, the tumors that formed from PGRMC1-deplete ovarian cancer cells were about a fourth the size of tumors derived from ovarian cancer cells with normal levels of PGRMC1. One reason for PGRMC1-deplete tumors being smaller is that they had a poorly developed microvasculature system. How PGRMC1 regulates cell viability and in turn tumor growth is not known but part of the mechanism likely involves the regulation of genes that promote cell survival and inhibit apoptosis. Copyright © 2011 Elsevier Inc. All rights reserved.

Control theory for scanning probe microscopy revisited.

PubMed

Stirling, Julian

2014-01-01

We derive a theoretical model for studying SPM feedback in the context of control theory. Previous models presented in the literature that apply standard models for proportional-integral-derivative controllers predict a highly unstable feedback environment. This model uses features specific to the SPM implementation of the proportional-integral controller to give realistic feedback behaviour. As such the stability of SPM feedback for a wide range of feedback gains can be understood. Further consideration of mechanical responses of the SPM system gives insight into the causes of exciting mechanical resonances of the scanner during feedback operation.

Scaffold hopping: exploration of acetanilide-containing uracil analogues as potential NNRTIs.

PubMed

Babkov, Denis A; Valuev-Elliston, Vladimir T; Paramonova, Maria P; Ozerov, Alexander A; Ivanov, Alexander V; Chizhov, Alexander O; Khandazhinskaya, Anastasia L; Kochetkov, Sergey N; Balzarini, Jan; Daelemans, Dirk; Pannecouque, Christophe; Seley-Radtke, Katherine L; Novikov, Mikhail S

2015-03-01

In order to identify novel nonnucleoside inhibitors of HIV-1 reverse transcriptase two series of amide-containing uracil derivatives were designed as hybrids of two scaffolds of previously reported inhibitors. Subsequent biological evaluation confirmed acetamide uracil derivatives 15a-k as selective micromolar NNRTIs with a first generation-like resistance profile. Molecular modeling of the most active compounds 15c and 15i was employed to provide insight on their inhibitory properties and direct future design efforts. Copyright © 2015 Elsevier Ltd. All rights reserved.

Evaluation of some significant issues affecting trajectory and control management for air-breathing hypersonic vehicles

NASA Technical Reports Server (NTRS)

Hattis, Philip D.; Malchow, Harvey L.

1992-01-01

Horizontal takeoff airbreathing-propulsion launch vehicles require near-optimal guidance and control which takes into account performance sensitivities to atmospheric characteristics while satisfying physically-derived operational constraints. A generic trajectory/control analysis tool that deepens insight into these considerations has been applied to two versions of a winged-cone vehicle model. Information that is critical to the design and trajectory of these vehicles is derived, and several unusual characteristics of the airbreathing propulsion model are shown to have potentially substantial effects on vehicle dynamics.

Determinants of patient-rated and clinician-rated illness severity in schizophrenia.

PubMed

Fervaha, Gagan; Takeuchi, Hiroyoshi; Agid, Ofer; Lee, Jimmy; Foussias, George; Remington, Gary

2015-07-01

The contribution of specific symptoms on ratings of global illness severity in patients with schizophrenia is not well understood. The present study examined the clinical determinants of clinician and patient ratings of overall illness severity. This study included 1,010 patients with a DSM-IV diagnosis of schizophrenia who participated in the baseline visit of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study conducted between January 2001 and December 2004 and who had available symptom severity, side effect burden, cognition, and community functioning data. Both clinicians and patients completed the 7-point Clinical Global Impressions-Severity of Illness scale (CGI-S), the primary measure of interest in the present study. Symptoms were rated using the Positive and Negative Syndrome Scale and the Calgary Depression Scale for Schizophrenia, and functional status with the Quality of Life Scale. Neurocognition, insight, and medication-related side effects were also evaluated. Clinicians rated illness severity significantly higher than patients (P < .001). There was moderate overlap between CGI-S ratings made by clinicians and patients, with almost one third of patients showing substantial (ie, greater than 1 point) discrepancies with clinician ratings. Clinician-rated CGI-S scores were most strongly associated with positive symptoms, with additional independent contributions made by negative, disorganized, and depressive symptoms, as well as functional outcome (all P values < .01). Patient-rated CGI-S scores, on the other hand, were most closely related to depressive symptoms, with additional independent contributions made by positive and anxiety symptoms, clinical insight, and neurocognition (all P values < .01). Depressive symptoms were the strongest predictor of patient-rated CGI-S scores even in patients with good clinical insight (P < .001). Patient and clinician views of overall illness severity are not necessarily interchangeable and differ in their clinical correlates. Taking these differences into account may enhance patient engagement in care and improve outcomes. ClinicalTrials.gov identifier: NCT00014001. © Copyright 2014 Physicians Postgraduate Press, Inc.

Suicidality in first episode psychosis is associated with insight and negative beliefs about psychosis.

PubMed

Barrett, Elizabeth A; Sundet, Kjetil; Faerden, Ann; Agartz, Ingrid; Bratlien, Unni; Romm, Kristin Lie; Mork, Erlend; Rossberg, Jan Ivar; Steen, Nils Eiel; Andreassen, Ole A; Melle, Ingrid

2010-11-01

Suicidal behaviour is prevalent in psychotic disorders. Insight has been found to be associated with increased risk for suicidal behaviour, but not consistently. A possible explanation for this is that insight has different consequences for patients depending on their beliefs about psychosis. The present study investigated whether a relationship between insight, negative beliefs about psychosis and suicidality was mediated by depressive symptoms, and if negative beliefs about psychosis moderated the relationship between insight and suicidality in patients with a first episode of psychosis (FEP). One hundred ninety-four FEP-patients were assessed with a clinical interview for diagnosis, symptoms, functioning, substance use, suicidality, insight, and beliefs about psychosis. Nearly 46% of the patients were currently suicidal. Depressive symptoms, having a schizophrenia spectrum disorder, insight, and beliefs about negative outcomes for psychosis were independently associated with current suicidality; contradicting a mediating effect of depressive symptoms. Negative beliefs about psychosis did not moderate the effect of insight on current suicidality. The results indicate that more depressive symptoms, higher insight, and negative beliefs about psychosis increase the risk for suicidality in FEP-patients. The findings imply that monitoring insight should be part of assessing the suicide risk in patients with FEP, and that treating depression and counteracting negative beliefs about psychosis may possibly reduce the risk for suicidality. Copyright © 2010 Elsevier B.V. All rights reserved.

The influence of current mood state, number of previous affective episodes and predominant polarity on insight in bipolar disorder.

PubMed

de Assis da Silva, Rafael; Mograbi, Daniel C; Camelo, Evelyn Vieira Miranda; Peixoto, Ursula; Santana, Cristina Maria Teixeira; Landeira-Fernandez, Jesus; Morris, Robin G; Cheniaux, Elie

2017-11-01

Although many studies have explored the effect of current affective episodes on insight into bipolar disorder, the potential interaction between current mood state and previous affective episodes has not been consistently investigated. To explore the influence of dominant polarity, number of previous affective episodes and current affective state on insight in bipolar disorder patients in euthymia or mania. A total of 101 patients with bipolar disorder were recruited for the study, including 58 patients in euthymia (30 with no defined predominant polarity and 28 with manic predominant polarity) and 43 in mania (26 with no defined predominant polarity and 17 with manic predominant polarity). Patients underwent a clinical assessment and insight was evaluated through the Insight Scale for Affective Disorders. Bipolar disorder patients in mania had worse insight than those in euthymia, with no effect of dominant polarity. In addition, positive psychotic symptoms showed a significant effect on insight and its inclusion as a covariate eliminated differences related to mood state. Finally, the number of previous manic or depressive episodes did not correlate with insight level. Mania is a predictor of loss of insight into bipolar disorder. However, it is possible that its contribution is linked to the more frequent presence of psychotic symptoms in this state. Dominant polarity and number/type of previous affective episodes have a limited impact on insight.

Suicidal behavior and insight into illness among patients with schizophrenia spectrum disorders.

PubMed

Kao, Yu-Chen; Liu, Yia-Ping

2011-09-01

The purpose of the present study was to explore the relationship between suicidal behavior and socio-demographic and clinical factors, including insight into illness, in patients with schizophrenia spectrum disorders. We evaluated 104 inpatients using the Self-Appraisal of Illness Questionnaire (SAIQ) for insight assessment, several Beck-related symptoms rating scales, and the Positive and Negative Syndrome Scale (PANSS) for psychopathology. These patients were also evaluated for suicidal behavior and risk using the critical items of the Scale for Suicide Ideation (SSI) and lifetime suicide attempts. Patients with suicidal behavior generally had greater insight into illness than those who were non-suicidal. After controlling for depressive symptoms, the association of insight into illness with current suicidal ideation remained significant, whereas the association between insight and lifetime suicide attempts was no longer significant. As predicted, the regression analyses revealed that those with greater suicide risk had significantly higher levels of depressive symptoms and hopelessness and more lifetime suicide attempts. Moreover, greater insight into illness appeared to have a close, independent connection to suicidal behavior. Our findings suggest that depression, hopelessness, and greater insight into illness are major risk factors for suicide in patients with schizophrenia. It is plausible that depression mediates the relationship between greater insight into illness and suicidal behavior. Aggressive improvement of insight without the risk of deteriorating depressive symptoms may be warranted to reduce the risk of suicide.

Typology for Parents of Abused Children.

ERIC Educational Resources Information Center

Sloan, Michael P.; Meier, John H.

This paper reports an effort to classify parents of abused children according to existing and new typologies derived from parents' psychopathological personality profiles. Several previously reported typologies for abusive parents are reviewed and elaborated. In addition, reference is given to data and insights gained from an ongoing study of 50…

A Mouse Ependymoma Model Provides Molecular Insights into Tumor Formation.

PubMed

Pajtler, Kristian W; Pfister, Stefan M

2018-06-26

Ozawa et al. present a murine tumor model resembling the most frequent molecular group of human supratentorial ependymoma, ST-EPN-RELA. Their model shows RELA-fusion-based de novo ependymoma tumorigenesis in the forebrain derived from neural stem cells. Copyright © 2018. Published by Elsevier Inc.

Evidence-Based Practice and Evaluation: From Insight to Impact

ERIC Educational Resources Information Center

Dunsmuir, Sandra; Brown, Emma; Iyadurai, Suzi; Monsen, Jeremy

2009-01-01

With the growing emphasis on accountability and evidence-based practice, evaluation has become increasingly important in the contexts in which educational psychologists (EPs) practice. This paper describes a Target Monitoring and Evaluation (TME) system, derived from Goal Attainment Scaling (GAS) which was developed to evaluate outcomes of a wide…

The Child Whisperer

ERIC Educational Resources Information Center

Peters, Dane L.

2012-01-01

Unquestionably, Maria Montessori's insights into child development were both innate and learned, derived from her many years of working with children. Her work, practices, philosophy, and passion have staying power that, so far, spans a century and are a testament to her dedication and abilities. In this article, the author explains why he sees…

Unstable solitary-wave solutions of the generalized Benjamin-Bona-Mahony equation

DOE Office of Scientific and Technical Information (OSTI.GOV)

McKinney, W.R.; Restrepo, J.M.; Bona, J.L.

1994-06-01

The evolution of solitary waves of the gBBM equation is investigated computationally. The experiments confirm previously derived theoretical stability estimates and, more importantly, yield insights into their behavior. For example, highly energetic unstable solitary waves when perturbed are shown to evolve into several stable solitary waves.

Parents of Children with Disabilities: Telling a Different Story.

ERIC Educational Resources Information Center

Goddard, Jay A.; Lehr, Ron; Lapadat, Judith C.

2000-01-01

Explores the desconstructive view of disability through an analysis of stories using criteria derived from constructivist principles of narrative therapy. Parents' narratives define and deconstruct the dominant discourse about being the parent of a child with disabilities and reveal insights about the impact of stereotypic views of disability.…

Pythagoras' Canvas

ERIC Educational Resources Information Center

Musto, Garrod

2009-01-01

This article seeks to provide an insight into little known numerical methods for deriving meaning from ancient sacred texts to give an understanding of some of the symbolism contained in the wonderful artwork and sculptures of Venetian artist Tobia Rava. The author describes how he used Rava's artwork to inspire a multi-faceted mathematics…

Understanding the mechanism of action of triazine-phosphonate derivatives as flame retardants for cotton fabrics

USDA-ARS?s Scientific Manuscript database

Countless hours of research and studies on triazine, phosphonate and their combination have provided insightful information into their flame retardant properties on polymeric systems. However, only limited number of studies shed light on the mechanism of flame retardant cotton fabrics. The purpose...

The Physics of Osmos

ERIC Educational Resources Information Center

Vanden Heuvel, Andrew

2016-01-01

We describe an analysis of the conservation of momentum in the video game Osmos, which demonstrates that the potential of video game analysis extends far beyond kinematics. This analysis can serve as the basis of an inquiry momentum lab that combines interesting derivations, video-based data collection, and insights into the subtle decisions that…

ACCURACY OF THE 1992 NATIONAL LAND COVER DATASET AREA ESTIMATES: AN ANALYSIS AT MULTIPLE SPATIAL EXTENTS

EPA Science Inventory

Abstract for poster presentation:

Site-specific accuracy assessments evaluate fine-scale accuracy of land-use/land-cover(LULC) datasets but provide little insight into accuracy of area estimates of LULC

classes derived from sampling units of varying size. Additiona...

Locating Multiethnic Families in a Globalizing World

ERIC Educational Resources Information Center

Trask, Bahira Sherif

2013-01-01

To derive new insights into the growing number of multiethnic, immigrant, transnational families in the United States and abroad, we need to incorporate the concept of globalization into our analysis. As the world becomes increasingly interconnected, an ever-growing number of heterogeneous individuals are associating with each other and being…

Predictive value of self-stigma, insight, and perceived adverse effects of medication for the clinical outcomes in patients with depressive disorders.

PubMed

Yen, Cheng-Fang; Lee, Yu; Tang, Tze-Chun; Yen, Ju-Yu; Ko, Chih-Hung; Chen, Cheng-Chung

2009-03-01

The aims of this prospective study were to examine the predictive values of self-stigma, insight, and perceived adverse effects of medication for remission of depressive symptoms, suicidal risk, and medication adherence in patients with depressive disorders over a 1-year follow-up period. One hundred seventy-four participants who were in a state of obvious depression underwent an index interview to determine their degree of self-stigma, insight, and perceived adverse effects of medication. One year later, they were reassessed to determine the severity of their depressive symptoms, suicidal risk, and the level of the medication adherence, and their associations with the 3 possible predictors at the index interview were examined. The results of this study indicated that perceiving more severe adverse effects of medication at the index interview increased the risks of the nonremission of depressive symptoms, occurrence of suicidal ideation or attempt, and medication nonadherence in patients with depressive disorders in the 1-year period. However, the degrees of self-stigma and insight did not predict the severity of depressive symptoms, suicidal risk, or the level of the medication adherence. Based on the results of this study, we suggest that it is important for clinicians to prevent the occurrence of and to help patients manage the adverse effects of medication. We also suggest that further prospective studies are needed to examine the predictive values of self-stigma and insight for clinical outcomes and medication adherence.

Prognostic factors and outcome in anorexia nervosa: a follow-up study.

PubMed

Errichiello, Luca; Iodice, Davide; Bruzzese, Dario; Gherghi, Marco; Senatore, Ignazio

2016-03-01

Anorexia nervosa is an eating disorder characterized by food restriction, irrational fear of gaining weight and consequent weight loss. High mortality rates have been reported, mostly due to suicide and malnutrition. Good outcomes largely vary between 18 and 42%. We aimed to assess outcome and prognostic factors of a large group of patients with anorexia nervosa. Moreover we aimed to identify clusters of prognostic factors related to specific outcomes. We retrospectively reviewed data of 100 patients diagnosed with anorexia nervosa previously hospitalized in a tertiary level structure. Then we performed follow-up structured telephone interviews. We identified four dead patients, while 34% were clinically recovered. In univariate analysis, short duration of inpatient treatment (p = 0.003), short duration of disorder (p = 0.001), early age at first inpatient treatment (p = 0.025) and preserved insight (p = 0.029) were significantly associated with clinical recovery at follow-up. In multiple logistic regression analysis, duration of first inpatient treatment, duration of disorder and preserved insight maintained their association with outcome. Moreover multiple correspondence analysis and cluster analysis allowed to identify different typologies of patients with specific features. Notably, group 1 was characterized by two or more inpatient treatments, BMI ≤ 14, absence of insight, history of long-term inpatient treatments, first inpatient treatment ≥30 days. While group 4 was characterized by preserved insight, BMI ≥ 16, first inpatient treatment ≤14 days, no more than one inpatient treatment, no psychotropic drugs intake, duration of illness ≤4 years. We confirmed the association between short duration of inpatient treatment, short duration of disorder, early age at first inpatient treatment, preserved insight and clinical recovery. We also differentiated patients with anorexia nervosa in well-defined outcome groups according to specific clusters of prognostic factors. Our study might help clinicians to evaluate prognosis of patients with anorexia nervosa.

Differences in severity at admission for heart failure between rural and urban patients: the value of adding laboratory results to administrative data.

PubMed

Smith, Mark W; Owens, Pamela L; Andrews, Roxanne M; Steiner, Claudia A; Coffey, Rosanna M; Skinner, Halcyon G; Miyamura, Jill; Popescu, Ioana

2016-04-18

Rural/urban variations in admissions for heart failure may be influenced by severity at hospital presentation and local practice patterns. Laboratory data reflect clinical severity and guide hospital admission decisions and treatment for heart failure, a costly chronic illness and a leading cause of hospitalization among the elderly. Our main objective was to examine the role of laboratory test results in measuring disease severity at the time of admission for inpatients who reside in rural and urban areas. We retrospectively analyzed discharge data on 13,998 hospital discharges for heart failure from three states, Hawai'i, Minnesota, and Virginia. Hospital discharge records from 2008 to 2012 were derived from the State Inpatient Databases of the Healthcare Cost and Utilization Project, and were merged with results of laboratory tests performed on the admission day or up to two days before admission. Regression models evaluated the relationship between clinical severity at admission and patient urban/rural residence. Models were estimated with and without use of laboratory data. Patients residing in rural areas were more likely to have missing laboratory data on admission and less likely to have abnormal or severely abnormal tests. Rural patients were also less likely to be admitted with high levels of severity as measured by the All Patient Refined Diagnosis Related Groups (APR-DRG) severity subclass, derivable from discharge data. Adding laboratory data to discharge data improved model fit. Also, in models without laboratory data, the association between urban compared to rural residence and APR-DRG severity subclass was significant for major and extreme levels of severity (OR 1.22, 95% CI 1.03-1.43 and 1.55, 95% CI 1.26-1.92, respectively). After adding laboratory data, this association became non-significant for major severity and was attenuated for extreme severity (OR 1.12, 95% CI 0.94-1.32 and 1.43, 95% CI 1.15-1.78, respectively). Heart failure patients from rural areas are hospitalized at lower severity levels than their urban counterparts. Laboratory test data provide insight on clinical severity and practice patterns beyond what is available in administrative discharge data.

NCI-CPTAC DREAM Proteogenomics Challenge (Registration Now Open) | Office of Cancer Clinical Proteomics Research

Cancer.gov

Proteogenomics, integration of proteomics, genomics, and transcriptomics, is an emerging approach that promises to advance basic, translational and clinical research.  By combining genomic and proteomic information, leading scientists are gaining new insights due to a more complete and unified understanding of complex biological processes.

Mobile-Assisted Grammar Exercises: Effects on Self-Editing in L2 Writing

ERIC Educational Resources Information Center

Li, Zhi; Hegelheimer, Volker

2013-01-01

In this paper, we report on the development and implementation of a web-based mobile application, "Grammar Clinic," for an ESL writing class. Drawing on insights from the interactionist approach to Second Language Acquisition (SLA), the Noticing Hypothesis, and mobile-assisted language learning (MALL), "Grammar Clinic" was…

Violence in inpatients with schizophrenia: a prospective study.

PubMed

Arango, C; Calcedo Barba, A; González-Salvador; Calcedo Ordóñez, A

1999-01-01

Accurate evaluations of the dangers posed by psychiatric inpatients are necessary, although a number of studies have questioned the accuracy of violence prediction. In this prospective study, we evaluated several variables in the prediction of violence in 63 inpatients with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder. Nurses rated violent incidents with the Overt Aggression Scale. During hospitalization, sociodemographic variables, clinical history, neurological soft signs, community alcohol or drug abuse, and electroencephalographic abnormalities did not differ between violent and nonviolent groups. Violent patients had significantly more positive symptoms as measured by the Positive and Negative Syndrome Scale (PANSS), higher scores on the PANSS general psychopathology scale, and less insight in the different constructs assessed. A logistic regression was performed to discriminate between violent and nonviolent patients. Three variables entered the model: insight into symptoms, PANSS general psychopathology score, and violence in the previous week. The actuarial model correctly classified 84.13 percent of the sample; this result is significantly better than chance for the base rate of violence in this study. At hospital admission, clinical rather than sociodemographic variables were more predictive of violence. This finding has practical importance because clinical symptoms are amenable to therapeutic approaches. This study is the first to demonstrate that insight into psychotic symptoms is a predictor of violence in inpatients with schizophrenia.

Big data in health care: using analytics to identify and manage high-risk and high-cost patients.

PubMed

Bates, David W; Saria, Suchi; Ohno-Machado, Lucila; Shah, Anand; Escobar, Gabriel

2014-07-01

The US health care system is rapidly adopting electronic health records, which will dramatically increase the quantity of clinical data that are available electronically. Simultaneously, rapid progress has been made in clinical analytics--techniques for analyzing large quantities of data and gleaning new insights from that analysis--which is part of what is known as big data. As a result, there are unprecedented opportunities to use big data to reduce the costs of health care in the United States. We present six use cases--that is, key examples--where some of the clearest opportunities exist to reduce costs through the use of big data: high-cost patients, readmissions, triage, decompensation (when a patient's condition worsens), adverse events, and treatment optimization for diseases affecting multiple organ systems. We discuss the types of insights that are likely to emerge from clinical analytics, the types of data needed to obtain such insights, and the infrastructure--analytics, algorithms, registries, assessment scores, monitoring devices, and so forth--that organizations will need to perform the necessary analyses and to implement changes that will improve care while reducing costs. Our findings have policy implications for regulatory oversight, ways to address privacy concerns, and the support of research on analytics. Project HOPE—The People-to-People Health Foundation, Inc.

Petrogenesis of Igneous-Textured Clasts in Martian Meteorite Northwest Africa 7034

NASA Technical Reports Server (NTRS)

Santos, A. R.; Agee, C. B.; Humayun, M.; McCubbin, F. M.; Shearer, C. K.

2016-01-01

The martian meteorite Northwest Africa 7034 (and pairings) is a breccia that samples a variety of materials from the martian crust. Several previous studies have identified multiple types of igneous-textured clasts within the breccia [1-3], and these clasts have the potential to provide insight into the igneous evolution of Mars. One challenge presented by studying these small rock fragments is the lack of field context for this breccia (i.e., where on Mars it formed), so we do not know how many sources these small rock fragments are derived from or the exact formation his-tory of these sources (i.e., are the sources mantle de-rived melt or melts contaminated by a meteorite impactor on Mars). Our goal in this study is to examine specific igneous-textured clast groups to determine if they are petrogenetically related (i.e., from the same igneous source) and determine more information about their formation history, then use them to derive new insights about the igneous history of Mars. We will focus on the basalt clasts, FTP clasts (named due to their high concentration of iron, titanium, and phosphorous), and mineral fragments described by [1] (Fig. 1). We will examine these materials for evidence of impactor contamination (as proposed for some materials by [2]) or mantle melt derivation. We will also test the petrogenetic models proposed in [1], which are igneous processes that could have occurred regardless of where the melt parental to the clasts was formed. These models include 1) derivation of the FTP clasts from a basalt clast melt through silicate liquid immiscibility (SLI), 2) derivation of the FTP clasts from a basalt clast melt through fractional crystallization, and 3) a lack of petrogenetic relationship between these clast groups. The relationship between the clast groups and the mineral fragments will also be explored.

Salicylic acid metabolites and derivatives inhibit CDK activity: Novel insights into aspirin's chemopreventive effects against colorectal cancer

PubMed Central

Dachineni, Rakesh; Kumar, D. Ramesh; Callegari, Eduardo; Kesharwani, Siddharth S.; Sankaranarayanan, Ranjini; Seefeldt, Teresa; Tummala, Hemachand; Bhat, G. Jayarama

2017-01-01

Aspirin's potential as a drug continues to be evaluated for the prevention of colorectal cancer (CRC). Although multiple targets for aspirin and its metabolite, salicylic acid, have been identified, no unifying mechanism has been proposed to clearly explain its chemopreventive effects. Our goal here was to investigate the ability of salicylic acid metabolites, known to be generated through cytochrome P450 (CYP450) enzymes, and its derivatives as cyclin dependent kinase (CDK) inhibitors to gain new insights into aspirin's chemopreventive actions. Using in vitro kinase assays, for the first time, we demonstrate that salicylic acid metabolites, 2,3-dihydroxy-benzoic acid (2,3-DHBA) and 2,5-dihydroxybenzoic acid (2,5-DHBA), as well as derivatives 2,4-dihydroxybenzoic acid (2,4-DHBA), 2,6-dihydroxybenzoic acid (2,6-DHBA), inhibited CDK1 enzyme activity. 2,3-DHBA and 2,6-DHBA did not inhibit CDK2 and 4; however, both inhibited CDK-6 activity. Interestingly, another derivative, 2,4,6-trihydroxybenzoic acid (2,4,6-THBA) was highly effective in inhibiting CDK1, 2, 4 and 6 activity. Molecular docking studies showed that these compounds potentially interact with CDK1. Immunoblotting experiments showed that aspirin acetylated CDK1, and pre-incubation with salicylic acid and its derivatives prevented aspirin-mediated CDK1 acetylation, which supported the data obtained from molecular docking studies. We suggest that intracellularly generated salicylic acid metabolites through CYP450 enzymes within the colonic epithelial cells, or the salicylic acid metabolites generated by gut microflora may significantly contribute to the preferential chemopreventive effect of aspirin against CRC through inhibition of CDKs. This novel hypothesis and mechanism of action in aspirin's chemopreventive effects opens a new area for future research. In addition, structural modification to salicylic acid derivatives may prove useful in the development of novel CDK inhibitors in cancer prevention and treatment. PMID:29075787

[Effect of dilution on aggregation of nanoparticles of polycarboxylic derivative of fullerene C60].

PubMed

Bobylev, A G; Pen'kov, N V; Troshin, P A; Gudkov, S V

2015-01-01

In this work, we investigated the effect of dilution on aggregation of nanoparticles of the polycarboxylic derivative of fullerene C60. It is shown that the diminution of the concentration of PCDF-1 in aqueous medium leads to a decreased amount of aggregates of fullerene and an increased amount of single molecules. This can potentially interfere with the biological activity of a compound on one molecule basis. Addition of organic and inorganic salts to the aqueous medium with fullerene derivative leads to intense disaggregation of PCDF-1. The data obtained suggest an explanation of non-stoichiometric nature of neutralization of reactive oxygen species by derivatives of fullerenes, as well as provide new insight into the physical meaning of the work on the impact of nanoparticles at ultra-low concentrations on biological objects.

Flow force and torque on submerged bodies in lattice-Boltzmann methods via momentum exchange.

PubMed

Giovacchini, Juan P; Ortiz, Omar E

2015-12-01

We review the momentum exchange method to compute the flow force and torque on a submerged body in lattice-Boltzmann methods by presenting an alternative derivation. Our derivation does not depend on a particular implementation of the boundary conditions at the body surface, and it relies on general principles. After the introduction of the momentum exchange method in lattice-Boltzmann methods, some formulations were introduced to compute the fluid force on static and moving bodies. These formulations were introduced in a rather intuitive, ad hoc way. In our derivation, we recover the proposals most frequently used, in some cases with minor corrections, gaining some insight into the two most used formulations. At the end, we present some numerical tests to compare different approaches on a well-known benchmark test that support the correctness of the formulas derived.

Treating autoimmune disorders with venom-derived peptides.

PubMed

Shen, Bingzheng; Cao, Zhijian; Li, Wenxin; Sabatier, Jean-Marc; Wu, Yingliang

2017-09-01

The effective treatment of autoimmune diseases remains a challenge. Voltage-gated potassium Kv1.3 channels, which are expressed in lymphocytes, are a new therapeutic target for treating autoimmune disease. Consequently, Kv1.3 channel-inhibiting venom-derived peptides are a prospective resource for new drug discovery and clinical application. Area covered: Preclinical and clinical studies have produced a wealth of information on Kv1.3 channel-inhibiting venom-derived peptides, especially from venomous scorpions and sea anemones. This review highlights the advances in screening and design of these peptides with diverse structures and potencies. It focuses on representative strategies for improving peptide selectivity and discusses the preclinical research on those venom-derived peptides as well as their clinical developmental status. Expert opinion: Encouraging results indicate that peptides isolated from the venom of venomous animals are a large resource for discovering immunomodulators that act on Kv1.3 channels. Since the structural diversity of venom-derived peptides determines the variety of their pharmacological activities, the design and optimization of venom-peptides for improved Kv1.3 channel-specificity has been advanced through some representative strategies, such as peptide chemical modification, amino acid residue truncation and binding interface modulation. These advances should further accelerate research, development and the future clinical application of venom-derived peptides selectively targeting Kv1.3 channels.

Unraveling the insight paradox: One-year longitudinal study on the relationships between insight, self-stigma, and life satisfaction among people with schizophrenia spectrum disorders.

PubMed

Chio, Floria H N; Mak, Winnie W S; Chan, Randolph C H; Tong, Alan C Y

2018-01-30

The promotion of insight among people with schizophrenia spectrum disorders has posed a dilemma to service providers as higher insight has been linked to positive clinical outcomes but negative psychological outcomes. The negative meaning that people attached to the illness (self-stigma content) and the recurrence of such stigmatizing thoughts (self-stigma process) may explain why increased insight is associated with negative outcomes. The present study examined how the presence of high self-stigma content and self-stigma process may contribute to the negative association between insight and life satisfaction. A total of 181 people with schizophrenia spectrum disorders were assessed at baseline. 130 and 110 participants were retained and completed questionnaire at 6-month and 1-year follow-up, respectively. Results showed that baseline insight was associated with lower life satisfaction at 6-month when self-stigma process or self-stigma content was high. Furthermore, baseline insight was predictive of better life satisfaction at 1-year follow-up when self-stigma process was low. Findings suggested that the detrimental effects of insight can be a result from both the presence of cognitive content and habitual process of self-stigma. Future insight promotion interventions should also address self-stigma content and process among people with schizophrenia spectrum disorders so as to maximize the beneficial effects of insight. Copyright © 2018 Elsevier B.V. All rights reserved.

Depot-medication compliance for patients with psychotic disorders: the importance of illness insight and treatment motivation

PubMed Central

Noordraven, Ernst L; Wierdsma, André I; Blanken, Peter; Bloemendaal, Anthony FT; Mulder, Cornelis L

2016-01-01

Background Noncompliance is a major problem for patients with a psychotic disorder. Two important risk factors for noncompliance that have a severe negative impact on treatment outcomes are impaired illness insight and lack of motivation. Our cross-sectional study explored how they are related to each other and their compliance with depot medication. Methods Interviews were conducted in 169 outpatients with a psychotic disorder taking depot medication. Four patient groups were defined based on low or high illness insight and on low or high motivation. The associations between depot-medication compliance, motivation, and insight were illustrated using generalized linear models. Results Generalized linear model showed a significant interaction effect between motivation and insight. Patients with poor insight and high motivation for treatment were more compliant (94%) (95% confidence interval [CI]: 1.821, 3.489) with their depot medication than patients with poor insight and low motivation (61%) (95% CI: 0.288, 0.615). Patients with both insight and high motivation for treatment were less compliant (73%) (95% CI: 0.719, 1.315) than those with poor insight and high motivation. Conclusion Motivation for treatment was more strongly associated with depot-medication compliance than with illness insight. Being motivated to take medication, whether to get better or for other reasons, may be a more important factor than having illness insight in terms of improving depot-medication compliance. Possible implications for clinical practice are discussed. PMID:26893565

Natural and accelerated recovery from brain damage: experimental and theoretical approaches.

PubMed

Andersen, Richard A; Schieber, Marc H; Thakor, Nitish; Loeb, Gerald E

2012-03-01

The goal of the Caltech group is to gain insight into the processes that occur within the primate nervous system during dexterous reaching and grasping and to see whether natural recovery from local brain damage can be accelerated by artificial means. We will create computational models of the nervous system embodying this insight and explain a variety of clinically observed neurological deficits in human subjects using these models.

Comparison of carbon-sulfur and carbon-amine bond in therapeutic drug: 4β-S-aromatic heterocyclic podophyllum derivatives display antitumor activity

PubMed Central

Li, Jian-Long; Zhao, Wei; Zhou, Chen; Zhang, Ya-Xuan; Li, Hong-Mei; Tang, Ya-Ling; Liang, Xin-Hua; Chen, Tao; Tang, Ya-Jie

2015-01-01

Herein is a first effort to systematically study the significance of carbon-sulfur (C-S) and carbon-amine (C-NH) bonds on the antitumor proliferation activity of podophyllum derivatives and their precise mechanism of apoptosis. Compared with the derivative modified by a C-NH bond, the derivative modified by a C-S bond exhibited superior antitumor activity, the inhibition activity of target proteins tubulin or Topo II, cell cycle arrest, and apoptosis induction. Antitumor mechanistic studies showed that the death receptor and the mitochondrial apoptotic pathways were simultaneously activated by the C-S bond modified aromatic heterocyclic podophyllum derivatives with a higher cellular uptake percentage of 60–90% and induction of a higher level of reactive oxygen species (ROS). Only the mitochondrial apoptotic pathway was activated by the C-NH bond modified aromatic heterocyclic podophyllum derivatives, with a lower cellular uptake percentage of 40–50%. This study provided insight into effects of the C-S and C-NH bond modification on the improvement of the antitumor activity of Podophyllum derivatives. PMID:26443888

Human Clinical-Grade Parthenogenetic ESC-Derived Dopaminergic Neurons Recover Locomotive Defects of Nonhuman Primate Models of Parkinson's Disease.

PubMed

Wang, Yu-Kai; Zhu, Wan-Wan; Wu, Meng-Hua; Wu, Yi-Hui; Liu, Zheng-Xin; Liang, Ling-Min; Sheng, Chao; Hao, Jie; Wang, Liu; Li, Wei; Zhou, Qi; Hu, Bao-Yang

2018-06-07

Clinical application of stem cell derivatives requires clinical-grade cells and sufficient preclinical proof of safety and efficacy, preferably in primates. We previously successfully established a clinical-grade human parthenogenetic embryonic stem cell (hPESC) line, but the suitability of its subtype-specific progenies for therapy is not clear. Here, we compared the function of clinical-grade hPESC-derived midbrain dopaminergic (DA) neurons in two canonical protocols in a primate Parkinson's disease (PD) model. We found that the grafts did not form tumors and produced variable but apparent behavioral improvement for at least 24 months in most monkeys in both groups. In addition, a slight DA increase in the striatum correlates with significant functional improvement. These results demonstrated that clinical-grade hPESCs can serve as a reliable source of cells for PD treatment. Our proof-of-concept findings provide preclinical data for China's first ESC-based phase I/IIa clinical study of PD (ClinicalTrials.gov number NCT03119636). Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

The Neurocircuitry of Impaired Insight in Drug Addiction

PubMed Central

Goldstein, Rita Z.; Craig, A. D. (Bud); Bechara, Antoine; Garavan, Hugh; Childress, Anna Rose; Paulus, Martin P.; Volkow, Nora D.

2010-01-01

More than 80% of addicted individuals fail to seek treatment, which might reflect impairments in recognition of severity of disorder. Considered by some as intentional deception, such `denial' might instead reflect dysfunction of brain networks subserving insight and selfawareness. Here we review the scant literature on insight in addiction and integrate this perspective with the role of: (i) the insula in interoception, self-awareness and drug craving; (ii) the anterior cingulate in behavioral monitoring and response selection (relevant to disadvantageous choices in addiction); (iii) the dorsal striatum in automatic habit formation; and (iv) drug related stimuli that predict emotional behavior in addicted individuals, even without conscious awareness. We discuss implications for clinical treatment including the design of interventions to improve insight into illness severity in addiction. PMID:19716751

Relationship of depression with cognitive insight and socio-occupational outcome in patients with schizophrenia.

PubMed

Grover, Sandeep; Sahoo, Swapnajeet; Nehra, Ritu; Chakrabarti, Subho; Avasthi, Ajit

2017-05-01

To evaluate the prevalence of depression using different measures in patients with schizophrenia and to study the relationship of depression in schizophrenia with cognitive insight and clinical insight, disability and socio-occupational functioning. A total of 136 patients with schizophrenia were evaluated for depression, cognitive insight and socio-occupational functioning. Of the 136 patients included in the study, one-fourth ( N = 34; 25%) were found to have depression as per the Mini International Neuropsychiatric Interview (MINI). The prevalence of depression as assessed by Calgary Depression Scale for Schizophrenia (CDSS), Hamilton depression rating scale (HDRS) and Depressive Subscale of Positive and Negative Syndrome Scale (PANSS-D) was 23.5%, 19.9% and 91.9%, respectively. Among the different scales, CDSS has highest concordance with clinician's diagnosis. Sensitivity, specificity, positive predictive value and negative predictive value for CDSS was also higher than that noted for HDRS and PANSS-D. When those with and without depression as per clinician's diagnosis were compared, those with depression were found to have significantly higher scores on Positive and Negative Syndrome Scale (PANSS) positive and general psychopathology subscales, PANSS total score, participation restriction as assessed by P-scale and had lower level of functioning as assessed by Global Assessment of Functioning (GAF). No significant difference was noted on negative symptom subscale of PANSS, clinical insight as assessed on G-12 item of PANSS, disability as assessed by Indian Disability Evaluation and Assessment Scale (IDEAS) and socio-occupational functioning as assessed by Social and Occupational Functioning Assessment Scale (SOFS). In terms of cognitive insight, those with depression had significantly higher score for both the subscales, that is, self-reflective and self-certainty subscales as well as the mean composite index score. Our results suggest that one-fourth of patients with schizophrenia have depression, compared to HDRS and PANSS-D, CDSS has highest concordance with clinician's diagnosis of depression and presence of depression is related to cognitive insight.

The African Diaspora: History, Adaptation and Health

PubMed Central

Rotimi, Charles N.; Tekola-Ayele, Fasil; Baker, Jennifer L.; Shriner, Daniel

2017-01-01

The trans-Atlantic slave trade brought millions of Africans to the New World. Advances in genomics are providing novel insights into the history and health of Africans and the diasporan populations. Recent examples reviewed here include the unraveling of substantial hunter-gatherer and “Eurasian” admixtures across sub-Saharan Africa, expanding our understanding of ancestral African genetics; the global ubiquity of mixed ancestry; the revealing of African ancestry in Latin Americans that likely derived from the slave trade; and understanding of the ancestral backgrounds of APOL1 and LPL found to influence kidney disease and lipid levels, respectively, providing specific insights into disease etiology and health disparities. PMID:27644073